World Journal Of Biological Chemistry[JOURNAL]
Sun
200 papers
Chloroquine and hydroxychloroquine: Immunomodulatory effects in autoimmune diseases.
Al-Hamadani M, Darweesh M, Mohammadi S … +1 more , Al-Harrasi A
World J Biol Chem · 2025 Jun · PMID 40476257 · Full text
Chloroquine (CQ) and hydroxychloroquine (HCQ), originally developed as antimalarial drugs, have found a new purpose in treating various autoimmune diseases due to their immunomodulatory properties. These drugs work throu...
Chloroquine (CQ) and hydroxychloroquine (HCQ), originally developed as antimalarial drugs, have found a new purpose in treating various autoimmune diseases due to their immunomodulatory properties. These drugs work through multiple mechanisms, including inhibiting Toll-like receptor signaling, suppressing antigen presentation, and modulating autophagy. This review article provides a comprehensive analysis of the immunomodulatory effects of CQ and HCQ in several autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and others. We delve into the intricate mechanisms of action, highlighting the key immune cells involved and discussing the clinical implications of these drugs in managing autoimmune conditions. Our review covers the latest research and clinical trials, offering a comprehensive understanding of the therapeutic potential of CQ and HCQ in autoimmune diseases. We also discuss the challenges and controversies surrounding the use of these drugs, such as their long-term side effects and the need for personalized treatment approaches. By synthesizing current knowledge and identifying areas for future research, this review aims to provide a valuable resource for healthcare professionals and researchers involved in the management of autoimmune diseases.
Bioactivity of dressings based on platelet-rich plasma and Platelet-rich fibrin for tissue regeneration in animal model.
Sá-Oliveira JA, Vieira Geraldo M, Marques M … +6 more , Luiz RM, Krasinski Cestari F, Nascimento Lima I, De Souza TC, Zarpelon-Schutz AC, Teixeira KN
World J Biol Chem · 2025 Mar · PMID 40070854 · Full text
BACKGROUND: Skin wounds are common injuries that affect quality of life and incur high costs. A considerable portion of healthcare resources in Western countries is allocated to wound treatment, mainly using mechanical,...
BACKGROUND: Skin wounds are common injuries that affect quality of life and incur high costs. A considerable portion of healthcare resources in Western countries is allocated to wound treatment, mainly using mechanical, biological, or artificial dressings. Biological and artificial dressings, such as hydrogels, are preferred for their biocompatibility. Platelet concentrates, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), stand out for accelerating tissue repair and minimizing risks of allergies and rejection. This study developed PRF and PRP-based dressings to treat skin wounds in an animal model, evaluating their functionality and efficiency in accelerating the tissue repair process. AIM: To develop wound dressings based on platelet concentrates and evaluating their efficiency in treating skin wounds in Wistar rats. METHODS: Wistar rats, both male and female, were subjected to the creation of a skin wound, distributed into groups ( = 64/group), and treated with Carbopol (negative control); PRP + Carbopol; PRF + Carbopol; or PRF + CaCl + Carbopol, on days zero (D0), D3, D7, D14, and D21. PRP and PRF were obtained only from male rats. On D3, D7, D14, and D21, the wounds were analyzed for area, contraction rate, and histopathology of the tissue repair process. RESULTS: The PRF-based dressing was more effective in accelerating wound closure early in the tissue repair process (up to D7), while PRF + CaCl seemed to delay the process, as wound closure was not complete by D21. Regarding macroscopic parameters, animals treated with PRF + CaCl showed significantly more crusting (necrosis) early in the repair process (D3). In terms of histopathological parameters, the PRF group exhibited significant collagenization at the later stages of the repair process (D14 and D21). By D21, fibroblast proliferation and inflammatory infiltration were higher in the PRP group. Animals treated with PRF + CaCl experienced a more pronounced inflammatory response up to D7, which diminished from D14 onwards. CONCLUSION: The PRF-based dressing was effective in accelerating the closure of cutaneous wounds in Wistar rats early in the process and in aiding tissue repair at the later stages.
Therapeutic potential of elafibranor in alcohol-associated liver disease: Insights into macrophage modulation and fibrosis reduction.
Farhadi S, Mohammadi S, AlKindi AY … +1 more , Al-Amri IS
World J Biol Chem · 2025 Mar · PMID 40070853 · Full text
Alcohol-associated liver disease (ALD) is a major global health concern, contributing to liver injury, morbidity, and mortality. Elafibranor (EFN), a dual peroxisome proliferator-activated receptor α/δ agonist, has shown...
Alcohol-associated liver disease (ALD) is a major global health concern, contributing to liver injury, morbidity, and mortality. Elafibranor (EFN), a dual peroxisome proliferator-activated receptor α/δ agonist, has shown promise as a therapeutic candidate in preclinical studies. EFN reduces liver fibrosis by inhibiting lipid accumulation, apoptosis, and inflammatory pathways (LPS/TLR4/NF-κB), while enhancing autophagy and antioxidant responses. It also improves intestinal barrier function and modulates gut microbiota, reducing endotoxin-producing bacteria and increasing beneficial species. By strengthening the intestinal barrier and suppressing pro-inflammatory mediators like tumor necrosis factor-alpha and interleukin-6, EFN mitigates hepatic stellate cell activation and fibrogenic signaling. Macrophages play a central role in ALD progression, and EFN's ability to modulate macrophage activity further highlights its anti-inflammatory properties. This review emphasizes EFN's dual-targeted approach, addressing both hepatic and intestinal dysfunctions, distinguishing it from conventional ALD treatments. While preclinical results are promising, EFN remains under clinical investigation, with ongoing trials evaluating its safety and efficacy. Future research should focus on elucidating EFN's molecular mechanisms and advancing its clinical application to establish its therapeutic potential in human populations. EFN represents a novel, comprehensive strategy for ALD management, targeting both liver and gut pathologies.
Hmo1: A versatile member of the high mobility group box family of chromosomal architecture proteins.
Bi X
World J Biol Chem · 2024 Aug · PMID 39156122 · Full text
Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures, which is facilitated by linker histone H1. Formation of chromatin compacts and protects the genome, but al...
Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures, which is facilitated by linker histone H1. Formation of chromatin compacts and protects the genome, but also hinders DNA transactions. Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions. The high mobility group box (HMGB) proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion. They play a major role in chromatin dynamics. The (yeast hereafter) HMGB protein Hmo1 contains two HMGB motifs. However, unlike a canonical HMGB protein that has an acidic C-terminus, Hmo1 ends with a lysine rich, basic, C-terminus, resembling linker histone H1. Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions. For instance, Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones. Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins and acts to maintain a common topological architecture of genes in yeast genome. This minireview reviews the functions of Hmo1 and the underlying mechanisms, highlighting recent discoveries.
Protein arginine methyltransferase 6 is a novel substrate of protein arginine methyltransferase 1.
Cao MT, Feng Y, Zheng YG
World J Biol Chem · 2023 Oct · PMID 37901302 · Full text
BACKGROUND: Post-translational modifications play key roles in various biological processes. Protein arginine methyltransferases (PRMTs) transfer the methyl group to specific arginine residues. Both PRMT1 and PRMT6 have...
BACKGROUND: Post-translational modifications play key roles in various biological processes. Protein arginine methyltransferases (PRMTs) transfer the methyl group to specific arginine residues. Both PRMT1 and PRMT6 have emerges as crucial factors in the development and progression of multiple cancer types. We posit that PRMT1 and PRMT6 might interplay directly or in-directly in multiple ways accounting for shared disease phenotypes. AIM: To investigate the mechanism of the interaction between PRMT1 and PRMT6. METHODS: Gel electrophoresis autoradiography was performed to test the methyltranferase activity of PRMTs and characterize the kinetics parameters of PRMTs. Liquid chromatography-tandem mass spectrometryanalysis was performed to detect the PRMT6 methylation sites. RESULTS: In this study we investigated the interaction between PRMT1 and PRMT6, and PRMT6 was shown to be a novel substrate of PRMT1. We identified specific arginine residues of PRMT6 that are methylated by PRMT1, with R106 being the major methylation site. Combined biochemical and cellular data showed that PRMT1 downregulates the enzymatic activity of PRMT6 in histone H3 methylation. CONCLUSION: PRMT6 is methylated by PRMT1 and R106 is a major methylation site induced by PRMT1. PRMT1 methylation suppresses the activity of PRMT6.
evidence of Remdesivir action in blood coagulation cascade modulation in COVID-19 treatment.
Pagliarin LG, de Oliveira LM, Dos Anjos VNF … +6 more , de Souza CBT, Peiter GC, Façanha Wendel C, Dillmann Groto A, Freire de Melo F, Teixeira KN
World J Biol Chem · 2023 Jul · PMID 37547340 · Full text
BACKGROUND: Coronavirus disease 2019 (COVID-19) has demonstrated several clinical manifestations which include not only respiratory system issues but also liver, kidney, and other organ injuries. One of these abnormaliti...
BACKGROUND: Coronavirus disease 2019 (COVID-19) has demonstrated several clinical manifestations which include not only respiratory system issues but also liver, kidney, and other organ injuries. One of these abnormalities is coagulopathies, including thrombosis and disseminated intravascular coagulation. Because of this, the administration of low molecular weight heparin is required for patients that need to be hospitalized. In addition, Remdesivir is an antiviral that was used against Middle East Acute Respiratory Syndrome, Ebola, Acute Respiratory Syndrome, and other diseases, showing satisfactory results on recovery. Besides, there is evidence suggesting that this medication can provide a better prognosis for patients with COVID-19. AIM: To investigate the interaction between Remdesivir and clotting factors, pursuing a possibility of using it as medicine. METHODS: In this study, the 3D structures of angiotensin-converting enzyme 2 (ACE2), Factor I (fibrinogen), Factor II (prothrombin), Factor III (thromboplastin), Factor V (proaccelerin), Factor VII (proconvertin), Factor VIII (antihemophilic factor A), Factor IX (antihemophilic factor B), Factor X (Stuart-Prower factor), and Factor XI (precursor of thromboplastin (these structures are technically called receptors) were selected from the Protein Data Bank. The structures of the antivirals Remdesivir and Osetalmivir (these structures are called ligands) were selected from the PubChem database, while the structure of Atazanavir was selected from the ZINC database. The software AutoDock Tools (ADT) was used to prepare the receptors for molecular docking. Ions, peptides, water molecules, and other ones were removed from each ligand, and then, hydrogen atoms were added to the structures. The grid box was delimited and calculated using the same software ADT. A physiological environment with pH 7.4 is needed to make the ligands interact with the receptors, and still the software Marvin sketch (ChemAxon) was used to forecast the protonation state. To perform molecular docking, ADT and Vina software was connected. Using PyMol software and Discovery studio software from BIOVIA, it was possible to analyze the amino acid residues from receptors that were involved in the interactions with the ligands. Ligand tortions, atoms that participated in the interactions, and the type, strength, and duration of the interactions were also analyzed using those software. RESULTS: Molecular docking analysis showed that Remdesivir and ACE2 had an affinity energy of -8.8 kcal/moL, forming a complex with eight hydrogen bonds involving seven atoms of Remdesivir and five amino acid residues of ACE2. Remdesivir and prothrombin had an interaction with six hydrogen bonds involving atoms of the drug and five amino acid residues of the clotting factor. Similar to that, Remdesivir and thromboplastin presented interactions seven hydrogen bonds involving five atoms of the drug and four residues of the clotting factor. While Remdesivir and Factor V established a complex with seven hydrogen bonds between six antiviral atoms and six amino acid residues from the factor, and Factor VII connected with the drug by four hydrogen bonds, which involved three atoms of the drug and three residues of amino acids of the factor. The complex between Remdesivir and Factor IX formed an interaction 11 hydrophilic bonds with seven atoms of the drug and seven residues of the clotting factor, plus one electrostatic bond and three hydrophobic interactions. Factor X and Remdesivir had an affinity energy of -9.6 kcal/moL, and the complex presented 10 hydrogen bonds and 14 different hydrophobic interactions which involved nine atoms of the drug and 16 amino acid residues of the clotting factor. The interaction between Remdesivir and Factor XI formed five hydrogen bonds involving five amino acid residues of the clotting factor and five of the antiviral atoms. CONCLUSION: Because of the significant affinity, Remdesivir possibly could act in the severe acute respiratory syndrome coronavirus 2 infection blockade by interacting with ACE2 and concomitantly act in the modulation of the coagulation cascade preventing the hypercoagulable state.
Comparison of the conventional tube and erythrocyte-magnetized technology in titration of red blood cell alloantibodies.
He XH, Yan H, Wang CY … +7 more , Duan XY, Qiao JJ, Guo XJ, Zhao HB, Ren D, Li JS, Zhang Q
World J Biol Chem · 2023 May · PMID 37273684 · Full text
BACKGROUND: Erythrocyte alloantibodies are mainly produced after immune stimulation, such as blood transfusion, pregnancy, and transplantation, and are the leading causes of severe hemolytic transfusion reactions and dif...
BACKGROUND: Erythrocyte alloantibodies are mainly produced after immune stimulation, such as blood transfusion, pregnancy, and transplantation, and are the leading causes of severe hemolytic transfusion reactions and difficulty in blood grouping and matching. Therefore, antibody screening is critical to prevent and improve red cell alloantibodies. Routine tube assay is the primary detection method of antibody screening. Recently, erythrocyte-magnetized technology (EMT) has been increasingly used in clinical practice. This study intends to probe the application and efficacy of the conventional tube and EMT in red blood cell alloantibody titration to provide a reference for clinical blood transfusion. AIM: To investigate the application value of conventional tube and EMT in red blood cell alloantibody titration and enhance the safety of blood transfusion practice. METHODS: A total of 1298 blood samples were harvested from blood donors at the Department of Blood Transfusion of our hospital from March 2021 to December 2022. A 5 mL blood sample was collected in tubing, which was then cut, and the whole blood was put into a test tube for centrifugation to separate the serum. Different red blood cell blood group antibody titers were simultaneously detected using the tube polybrene test, tube antiglobulin test (AGT), and EMT screening irregular antibody methods to determine the best test method. RESULTS: Simultaneous detection was performed through the tube polybrene test, tube AGT and EMT screening irregular antibodies. It was discovered that the EMT screening irregular antibody method could detect all immunoglobulin G (IgG) and immunoglobulin M (IgM) irregular antibodies, and the results of manual tube AGT were satisfactory, but the operation time was lengthy, and the equipment had a large footprint. The EMT screening irregular antibody assay was also conducted to determine its activity against type O Rh (D) red blood cells, and the outcomes were satisfactory. Furthermore, compared to the conventional tube method, the EMT screening irregular antibody method was more cost-effective and had significantly higher detection efficiency. CONCLUSION: With a higher detection rate, the EMT screening irregular antibody method can detect both IgG and IgM irregular antibodies faster and more effectively than the conventional tube method.
Anticancer potential of and its constituents, a powerful plant for cancer therapy.
Sirizi MAG, Alizadeh Ghalenoei J, Allahtavakoli M … +2 more , Forouzanfar H, Bagheri SM
World J Biol Chem · 2023 Mar · PMID 37034135 · Full text
Cancer is one of the main challenges of the health system around the world. This disease is increasing in developing countries and imposes heavy costs on patients and governments. On the other hand, despite various drugs...
Cancer is one of the main challenges of the health system around the world. This disease is increasing in developing countries and imposes heavy costs on patients and governments. On the other hand, despite various drugs, the death rate among cancer patients is still high and the current treatments have many harmful effects. In the traditional medicine of different countries, there are many medicinal plants that can be effective in the treatment of cancer. Ferula plants are traditionally used as spices and food or for medicinal purposes. is one of the famous plants of this genus, which has been used for the treatment of various diseases since ancient times. Among the main compounds of this plant, we can mention monoterpenes, sulfide compounds and polyphenols, which can show different therapeutic effects. This article has been compiled with the aim of collecting evidence and articles related to the anti-cancer effects of extracts, derived compounds, essential oils and nanoparticles containing . This review article was prepared by searching the terms and cancer, and relevant information was collected through searching electronic databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Fortunately, the results of this review showed that relatively comprehensive studies have been conducted in this field and shown that can be very promising in the treatment of cancer.
Temporal pattern of humoral immune response in mild cases of COVID-19.
Pilati Campos IM, Marques M, Peiter GC … +4 more , Brandalize APC, Dos Santos MB, de Melo FF, Teixeira KN
World J Biol Chem · 2023 Mar · PMID 37034134 · Full text
BACKGROUND: Understanding the humoral response pattern of coronavirus disease 2019 (COVID-19) is one of the essential factors to better characterize the immune memory of patients, which allows understanding the temporali...
BACKGROUND: Understanding the humoral response pattern of coronavirus disease 2019 (COVID-19) is one of the essential factors to better characterize the immune memory of patients, which allows understanding the temporality of reinfection, provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consequently helps in global public health and vaccination strategy. Among the patients who became infected with SARS-CoV-2, the majority who did not progress to death were those who developed the mild COVID-19, so understanding the pattern and temporality of the antibody response of these patients is certainly relevant. AIM: To investigate the temporal pattern of humoral response of specific immunoglobulin G (IgG) in mild cases of COVID-19. METHODS: Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction (RT-qPCR)-positive volunteers from the municipality of Toledo/ Paraná/Brazil, underwent two distinct serological tests, enzyme-linked immunosorbent assay, and detection of anti-nucleocapsid IgG. Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021. All assays were performed in duplicate and the manufacturers' recommendations were strictly followed. The data were statistically analyzed using multiple logistic regression; the variables were selected by applying the < 0.05 criterion. RESULTS: Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo. The time periods when the highest number of participants with detectable IgG was observed were 1, 2 and 3 mo. It was observed that 9.42% of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57% were also IgG negative at less than 1 mo. At 5 mo, 3.14% of volunteers were IgG negative, and at 6 or 7 mo, 1 volunteer (0.52%) had no detectable IgG. During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study, no statistical significance was observed for any association analyzed. Moreover, considering the age category between 31 and 59 years as the exposed group, the value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older, showing that in both age categories there was no association between the pair of variables analyzed. Regarding chronic disease, the exposure group consisted of the participants without any comorbidity, so the value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables. CONCLUSION: A temporal pattern of IgG response was not observed, but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.
Correlation of serum SARS-CoV-2 IgM and IgG serology and clinical outcomes in COVID-19 patients: Experience from a tertiary care centre.
Suresh M, Kumar P, Panda PK … +5 more , Jain V, Raina R, Saha S, Vivekanandhan S, Omar BJ
World J Biol Chem · 2023 Mar · PMID 37034133 · Full text
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has become a pandemic for the last 2 years. Inflammatory response to the virus leads to organ dysfunction and death. Predicting the sever...
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has become a pandemic for the last 2 years. Inflammatory response to the virus leads to organ dysfunction and death. Predicting the severity of inflammatory response helps in managing critical patients using serology tests IgG and IgM. AIM: To investigate the correlation of the serology (IgM and IgG) with reverse transcriptase polymerase chain reaction (RT-PCR) status, disease severity [mild to critical], intensive care unit (ICU) admission, septic shock, acute kidney injury, and in-hospital mortality. METHODS: We conducted a longitudinal study to correlate serum SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) serology with clinical outcomes in coronavirus disease 2019 (COVID-19) patients. We analyzed patient data from March to December 2020 for those who were admitted at All India Institute of Medical Sciences Rishikesh. Clinical and laboratory data of these patients were collected from the e-hospital portal and analyzed. A correlation was seen with clinical outcomes and was assessed using MS Excel 2010 and SPSS software. RESULTS: Out of 494 patients, the mean age of patients was 48.95 ± 16.40 years and there were more male patients in the study (66.0%). The patients were classified as mild-moderate 328 (67.1%), severe 131 (26.8%), and critical 30 (6.1%). The mean duration from symptom onset to serology testing was 19.87 ± 30.53 d. In-hospital mortality was observed in 25.1% of patients. The seropositivity rate (, either IgG or IgM > 10 AU) was 50%. IgM levels (AU/mL) (W = 33428.000, ≤ 0.001) and IgG levels (AU/mL) (W = 39256.500, ≤ 0.001), with the median IgM/ IgG levels (AU/mL), were highest in the RT-PCR-Positive group compared to RT-PCR-Negative clinical COVID-19. There was no significant difference between the two groups in terms of all other clinical outcomes (disease severity, septic shock, ICU admission, mechanical ventilation, and mortality). CONCLUSION: The study showed that serology levels are high in RT-PCR positive group compared to clinical COVID-19. However, serology cannot be useful for the prediction of disease outcomes. The study also highlights the importance of doing serology at a particular time as antibody titers vary with the duration of the disease. In week intervals there was a significant correlation between clinical outcomes and serology on week 3.
Molecular genetics of early-onset colorectal cancer.
Marx O, Mankarious M, Yochum G
World J Biol Chem · 2023 Mar · PMID 37034132 · Full text
Early-onset colorectal cancer (EOCRC) has been rising in global prevalence and incidence over the past several decades. Environmental influences, including generational lifestyle changes and rising obesity, contribute to...
Early-onset colorectal cancer (EOCRC) has been rising in global prevalence and incidence over the past several decades. Environmental influences, including generational lifestyle changes and rising obesity, contribute to these increased rates. While the rise in EOCRC is best documented in western countries, it is seen throughout the world, although EOCRC may have distinct genetic mutations in patients of different ethnic backgrounds. Pathological and molecular characterizations show that EOCRC has a distinct presentation compared with later-onset colorectal cancer (LOCRC). Recent studies have identified DNA, RNA, and protein-level alterations unique to EOCRC, revealing much-needed biomarkers and potential novel therapeutic targets. Many molecular EOCRC studies have been performed with Caucasian and Asian EOCRC cohorts, however, studies of other ethnic backgrounds are limited. In addition, certain molecular characterizations that have been conducted for LOCRC have not yet been repeated in EOCRC, including high-throughput analyses of histone modifications, mRNA splicing, and proteomics on large cohorts. We propose that the complex relationship between cancer and aging should be considered when studying the molecular underpinnings of EOCRC. In this review, we summarize current EOCRC literature, focusing on sporadic molecular alterations in tumors, and their clinical implications. We conclude by discussing current challenges and future directions of EOCRC research efforts.
Marine biological injuries and their medical management: A narrative review.
Geng XY, Wang MK, Chen JH … +2 more , Xiao L, Yang JS
World J Biol Chem · 2023 Jan · PMID 36741876 · Full text
The marine environment can be extremely dangerous, and the harm caused by marine organisms when they contact the human body can be especially harmful, even deadly. Contact includes stings, bites, wounds, and consumption...
The marine environment can be extremely dangerous, and the harm caused by marine organisms when they contact the human body can be especially harmful, even deadly. Contact includes stings, bites, wounds, and consumption as food. In this article, the characteristics of the common marine biological injuries are summarized, the major marine organisms causing damage in China's marine waters are described, and injury prevention and treatment methods are discussed.
Serum leptin level in Sudanese women with unexplained infertility and its relationship with some reproductive hormones.
Abdulslam Abdullah A, Ahmed M, Oladokun A … +2 more , Ibrahim NA, Adam SN
World J Biol Chem · 2022 Nov · PMID 36482982 · Full text
BACKGROUND: The excessive concentration of leptin has negative effects on all aspects of female reproduction. Despite this established relationship, the exact role of leptin in women's fertility is not clear enough and n...
BACKGROUND: The excessive concentration of leptin has negative effects on all aspects of female reproduction. Despite this established relationship, the exact role of leptin in women's fertility is not clear enough and needs more clarification. AIM: To evaluate the serum leptin levels in Sudanese women and to ascertain the relationship between serum leptin levels and unexplained infertility (UI). METHODS: A matched (age and body mass index) case-control study was conducted from March 2021 to February 2022. The study samples were 210 women with UI and 190 fertile women of reproductive age who were attending the maternity hospitals and fertility clinics in Khartoum state Sudan. The serum concentration of leptin and other serum biomarkers were determined using enzyme-linked immunosorbent assays. RESULTS: The results showed that there was a highly statistically significant difference between the two groups ( < 0.001) for all examined eight biomarkers. Whereby, leptin, luteinizing hormone (LH)/follicular stimulating hormone (FSH) ratio, prolactin hormone (PRL) and testosterone (T) were significantly higher in the UI group compared with the control group. In contrast, FSH and estradiol (E2)/T ratio were significantly lower in the UI group than in the control group and the effect size test for the difference between the two groups was very large (effect size > 0.80), for leptin level, LH/FSH ratio, PRL level, and E2/T ratio, and large (effect size 0.50- ≤ 0.80) for FSH and T. CONCLUSION: This study reveals that leptin could be a potential biomarker for UI in Sudanese women and it may be useful for identifying women with a high risk of infertility.
Profiles of interferon-gamma and interleukin-2 in patients after allogeneic hematopoietic stem cell transplantation.
Rybicka-Ramos M, Markiewicz M, Suszka-Świtek A … +4 more , Wiaderkiewicz R, Mizia S, Dzierżak-Mietła M, Białas K
World J Biol Chem · 2022 Sep · PMID 36187719 · Full text
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be related to the occurrence of complications, including graft-versus-host disease (GvHD) and infections. The pathogenesis of acute GvHD is c...
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be related to the occurrence of complications, including graft-versus-host disease (GvHD) and infections. The pathogenesis of acute GvHD is connected with T lymphocytes, which identify alloantigens on host's antigen-presenting cells, activate production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), and act on the immune effector cells and damage tissues and organs. AIM: The aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after allo-HSCT. METHODS: We enrolled 62 patients, , 30 (48%) male and 32 (52%) female subjects [median age 49.5 (19-68) years], after allo-HSCT from siblings ( = 12) or unrelated donors ( = 50) due to acute myeloid leukemia with myeloablative conditioning ( = 26; 42%) and with non-myeloablative conditioning ( = 36; 58%). All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated setting. Blood samples were collected pre-transplant before and after (on day -1) the conditioning therapy and on days +2,+4, +6, +10, +20, and +30 after allo-HSCT. Serum levels of IL-2 and IFN-gamma were determined using ELISA. RESULTS: Patients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of infection. Group I included patients with neither acute GvHD nor infections [ = 15 (24%)], group II consisted of patients with infections without acute GvHD [ = 17 (27%)], group III was comprised of patients with acute GvHD without infections [ = 9 (15%)], and group IV included patients with both acute GvHD and infections [ = 21 (34%)]. IFN-gamma concentrations were higher in Group II than in other groups on days +20 ( = 0.014) and +30 ( = 0.008). Post-hoc tests showed lower concentrations of IFN-gamma on day +30 in groups I ( = 0.039) and IV ( = 0.017) compared to group II. The levels of IL-2 were mostly undetectable. CONCLUSION: Serum levels of IFN-gamma following allo-HSCT progressively escalate. High serum levels of IFN-gamma are related to infectious complications rather than acute GvHD. Serum concentrations of IL-2 in most patients are undetectable.
Progesterone in gender-affirming therapy of trans women.
Milionis C, Ilias I, Koukkou E
World J Biol Chem · 2022 May · PMID 35721880 · Full text
Progesterone is an endogenous steroid hormone with an important role for the physiology of the female reproductive system and the mammary gland. It has additional significant actions in other tissues, such as the cardiov...
Progesterone is an endogenous steroid hormone with an important role for the physiology of the female reproductive system and the mammary gland. It has additional significant actions in other tissues, such as the cardiovascular system, the central nervous system, and bones. The present article explores potential clinical implications from the addition of bioidentical progesterone to gender-affirming treatment of trans women. For this purpose, it provides an overview of the physiological action of progesterone in target tissues and speculates on possible benefits for gender transitioning. Progesterone is expected to exert moderate anti-androgen action through suppression of the hypothalamic-pituitary-gonadal axis and inhibition of the conversion of testosterone to dihydrotestosterone. It may also contribute to breast maturation. In the long-term, progesterone could prevent bone loss and protect cardiovascular health. The potential benefits are mainly inferred by extrapolating evidence from biological actions in cisgender women and medical assumptions and hence, clinicians need to be cautious when applying these data into practice. Further research is needed to ascertain the efficacy and safety of progesterone in current hormonal regimens.
Mesenchymal stromal cell delivery as a potential therapeutic strategy against COVID-19: Promising evidence from results.
Mallis P, Chatzistamatiou T, Dimou Z … +7 more , Sarri EF, Georgiou E, Salagianni M, Triantafyllia V, Andreakos E, Stavropoulos-Giokas C, Michalopoulos E
World J Biol Chem · 2022 Mar · PMID 35432769 · Full text
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic, which was initiated in December 2019. COVID-19 is characterized by a low morta...
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic, which was initiated in December 2019. COVID-19 is characterized by a low mortality rate (< 6%); however, this percentage is higher in elderly people and patients with underlying disorders. COVID-19 is characterized by mild to severe outcomes. Currently, several therapeutic strategies are evaluated, such as the use of anti-viral drugs, prophylactic treatment, monoclonal antibodies, and vaccination. Advanced cellular therapies are also investigated, thus representing an additional therapeutic tool for clinicians. Mesenchymal stromal cells (MSCs), which are known for their immunoregulatory properties, may halt the induced cytokine release syndrome mediated by SARS-CoV-2, and can be considered as a potential stem cell therapy. AIM: To evaluate the immunoregulatory properties of MSCs, upon stimulation with COVID-19 patient serum. METHODS: MSCs derived from the human Wharton's Jelly (WJ) tissue and bone marrow (BM) were isolated, cryopreserved, expanded, and defined according to the criteria outlined by the International Society for Cellular Therapies. Then, WJ and BM-MSCs were stimulated with a culture medium containing 15% COVID-19 patient serum, 1% penicillin-streptomycin, and 1% L-glutamine for 48 h. The quantification of interleukin (IL)-1 receptor a (Ra), IL-6, IL-10, IL-13, transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF)-a, fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and indoleamine-2,3-dioxygenase (IDO) was performed using commercial ELISA kits. The expression of HLA-G1, G5 and G7 was evaluated in unstimulated and stimulated WJ and BM-MSCs. Finally, the interactions between MSCs and patients' macrophages were established using co-culture experiments. RESULTS: Thawed WJ and BM-MSCs exhibited a spindle-shaped morphology, successfully differentiated to "osteocytes", "adipocytes", and "chondrocytes", and in flow cytometric analysis were characterized by positivity for CD73, CD90, and CD105 (> 95%) and negativity for CD34, CD45, and HLA-DR (< 2%). Moreover, stimulated WJ and BM-MSCs were characterized by increased cytoplasmic granulation, in comparison to unstimulated cells. The HLA-G isoforms (G1, G5, and G7) were successfully expressed by the unstimulated and stimulated WJ-MSCs. On the other hand, only weak expression of HLA-G1 was identified in BM-MSCs. Stimulated MSCs secreted high levels of IL-1Ra, IL-6, IL-10, IL-13, TGF-β1, FGF, VEGF, PDGF, and IDO in comparison to unstimulated cells ( < 0.05) after 12 and 24 h. Finally, macrophages derived from COVID-19 patients successfully adapted the M2 phenotype after co-culturing with stimulated WJ and BM-MSCs. CONCLUSION: WJ and BM-MSCs successfully produced high levels of immunoregulatory agents, which may efficiently modulate the over-activated immune responses of critically ill COVID-19 patients.
LIN28A: A multifunctional versatile molecule with future therapeutic potential.
Wu K, Ahmad T, Eri R
World J Biol Chem · 2022 Mar · PMID 35432768 · Full text
An RNA-binding protein, LIN28A was initially discovered in nematodes and regulated stem cell differentiation and proliferation. With the aid of mouse models and cancer stem cells models, LIN28A demonstrated a similar ro...
An RNA-binding protein, LIN28A was initially discovered in nematodes and regulated stem cell differentiation and proliferation. With the aid of mouse models and cancer stem cells models, LIN28A demonstrated a similar role in mammalian stem cells. Subsequent studies revealed LIN28A's roles in regulating cell cycle and growth, tissue repair, and metabolism, especially glucose metabolism. Through regulation by pluripotency and neurotrophic factors, LIN28A performs these roles through dependent (binding to ) or independent (binding directly to mature mRNA) pathways. Elevated LIN28A levels are associated with cancers such as breast, colon, and ovarian cancers. Overexpressed LIN28A has been implicated in liver diseases and Rett syndrome whereas loss of LIN28A was linked to Parkinson's disease. LIN28A inhibitors, LIN28A-specific nanobodies, and deubiquitinases targeting LIN28A could be feasible options for cancer treatments while drugs upregulating LIN28A could be used in regenerative therapy for neuropathies. We will review the upstream and downstream signalling pathways of LIN28A and its physiological functions. Then, we will examine current research and gaps in research regarding its mechanisms in conditions such as cancers, liver diseases, and neurological diseases. We will also look at the therapeutic potential of LIN28A in RNA-targeted therapies including small interfering RNAs and RNA-protein interactions.
Increased monoamine oxidase activity and imidazoline binding sites in insulin-resistant adipocytes from obese Zucker rats.
Carpéné C, Marti L, Morin N
World J Biol Chem · 2022 Jan · PMID 35126867 · Full text
BACKGROUND: Despite overt insulin resistance, adipocytes of genetically obese Zucker rats accumulate the excess of calorie intake in the form of lipids. AIM: To investigate whether factors can replace or reinforce insuli...
BACKGROUND: Despite overt insulin resistance, adipocytes of genetically obese Zucker rats accumulate the excess of calorie intake in the form of lipids. AIM: To investigate whether factors can replace or reinforce insulin lipogenic action by exploring glucose uptake activation by hydrogen peroxide, since it is produced by monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) in adipocytes. METHODS: H-2-deoxyglucose uptake (2-DG) was determined in adipocytes from obese and lean rats in response to insulin or MAO and SSAO substrates such as tyramine and benzylamine. C-tyramine oxidation and binding of imidazolinic radioligands [H-Idazoxan, H-(2-benzofuranyl)-2-imidazoline] were studied in adipocytes, the liver, and muscle. The influence of administration of tyramine + vanadium on glucose handling was assessed in lean and obese rats. RESULTS: 2-DG uptake and lipogenesis stimulation by insulin were dampened in adipocytes from obese rats, when compared to their lean littermates. Tyramine and benzylamine activation of hexose uptake was vanadate-dependent and was also limited, while MAO was increased and SSAO decreased. These changes were adipocyte-specific and accompanied by a greater number of imidazoline I binding sites in the obese rat, when compared to the lean. , tyramine precluded the binding to I sites, while , its administration together with vanadium lowered fasting plasma levels of glucose and triacylglycerols in obese rats. CONCLUSION: The adipocytes from obese Zucker rats exhibit increased MAO activity and imidazoline binding site number. However, probably as a consequence of SSAO down-regulation, the glucose transport stimulation by tyramine is decreased as much as that of insulin in these insulin-resistant adipocytes. The adipocyte amine oxidases deserve more studies with respect to their putative contribution to the management of glucose and lipid handling.
Current understanding of the role of tyrosine kinase 2 signaling in immune responses.
Muromoto R, Oritani K, Matsuda T
World J Biol Chem · 2022 Jan · PMID 35126866 · Full text
Immune system is a complex network that clears pathogens, toxic substrates, and cancer cells. Distinguishing self-antigens from non-self-antigens is critical for the immune cell-mediated response against foreign antigens...
Immune system is a complex network that clears pathogens, toxic substrates, and cancer cells. Distinguishing self-antigens from non-self-antigens is critical for the immune cell-mediated response against foreign antigens. The innate immune system elicits an early-phase response to various stimuli, whereas the adaptive immune response is tailored to previously encountered antigens. During immune responses, B cells differentiate into antibody-secreting cells, while naïve T cells differentiate into functionally specific effector cells [T helper 1 (Th1), Th2, Th17, and regulatory T cells]. However, enhanced or prolonged immune responses can result in autoimmune disorders, which are characterized by lymphocyte-mediated immune responses against self-antigens. Signal transduction of cytokines, which regulate the inflammatory cascades, is dependent on the members of the Janus family of protein kinases. Tyrosine kinase 2 (Tyk2) is associated with receptor subunits of immune-related cytokines, such as type I interferon, interleukin (IL)-6, IL-10, IL-12, and IL-23. Clinical studies on the therapeutic effects and the underlying mechanisms of Tyk2 inhibitors in autoimmune or chronic inflammatory diseases are currently ongoing. This review summarizes the findings of studies examining the role of Tyk2 in immune and/or inflammatory responses using -deficient cells and mice.
Remission is not maintained over 2 years with hematopoietic stem cell transplantation for rheumatoid arthritis: A systematic review with meta-analysis.
Muthu S, Jeyaraman M, Ranjan R … +1 more , Jha SK
World J Biol Chem · 2021 Nov · PMID 34904049 · Full text
BACKGROUND: Hematopoietic stem cell (HSC) transplantation (HSCT) is being accepted as a standard of care in various inflammatory diseases. The treatment of rheumatoid arthritis (RA) has been closely evolving with the und...
BACKGROUND: Hematopoietic stem cell (HSC) transplantation (HSCT) is being accepted as a standard of care in various inflammatory diseases. The treatment of rheumatoid arthritis (RA) has been closely evolving with the understanding of disease pathogenesis. With the rising resistance to the traditional disease-modifying anti-rheumatic drugs and targeted biological therapy, researchers are in pursuit of other methods for disease management. Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance, HSCT attracts much attention considering its reparative, paracrine, and anti-inflammatory effects. However, a systematic review of studies on HSCT in RA is lacking. AIM: To investigate the role of HSCT in the management of RA. METHODS: A detailed search of PubMed, Scopus, EMBASE, Cochrane, and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines. We extracted data including the number of patients, source of hematopoietic stem cells, their mobilization and conditioning regimens, results, and complications from the eligible studies. Results were dichotomized into success (ACR 50/70) and failure (ACR 20) based on the improvement from baseline characteristics. The methodological quality of the included studies was also assessed. Analysis was performed using OpenMeta[Analysis] software. RESULTS: We included 17 studies (1 randomized controlled trial, 11 prospective, and 5 retrospective studies) with 233 patients for analysis. HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria ( = 11.309, 0.001). However, the remission was noted only till 24 mo and later on the significance of the result was lost ( = 1.737, = 0.082). A less than 1% treatment-related mortality was noted from the included studies. No major drug-related toxicities were noted in any of the included studies. All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft--host reaction which made them vulnerable to infections. It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous ( = 9.972, 0.001) and allogenic ( = 6.978, 0.001) sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them ( = 99.4, 0.001). CONCLUSION: Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years, the inclusion of HSCT into the standard of care of RA needs further exploration.
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