Discovery Medicine[JOURNAL]
Sun
200 papers
Characterization of Metronidazole, Clarithromycin and Amoxicillin Resistance Genes in Isolated from Gastroenteritis Patients.
Iqbal S, Ullah W, Shah SF … +2 more , Gul A, Basit A
Discov Med · 2024 Sep · PMID 39327248 · Publisher ↗
BACKGROUND: ()is a Gram-negative, microaerophilic, and spiral shape bacterium that resides inside the human stomach. The human stomach serves as its primary reservoir. Complaints about stomach complication due to infec...
BACKGROUND: ()is a Gram-negative, microaerophilic, and spiral shape bacterium that resides inside the human stomach. The human stomach serves as its primary reservoir. Complaints about stomach complication due to infections are reported in the majority of populations around the globe. Chronic gastritis and intestinal metaplasia of the gastric mucosa are major complications of a long-term infections that can lead to gastric cancer in severe cases. This study aims to characterize isolates from gastroenteritis patients and to determine the resistance of to various antibiotics. METHODS: In the current study, a total of (n = 80) gastric biopsy samples were randomly collected from gastroenteritis patients in brain-heart infusion broth. These were inoculated on Columbia blood agar supplemented with selective supplement (DENT). After culturing, Microscopy and biochemical tests were performed. The susceptibility profile of isolates was evaluated using the Kirby Bauer disk diffusion method. On the basis of the drug resistance profile, a total of (n = 20) isolates including (n = 10) from females and (n = 10) from males were selected for the detection and characterization of resistant genes. After confirmation of using , polymerase chain reaction (PCR) was done for the detection of resistance genes including Metronidazole resistance ( gene), Clarithromycin resistance ( gene) and Amoxicillin resistance (Penicillin-binding protein A1 () gene). RESULTS: In a total of (n = 80) samples, was isolated from 72.5% (n = 58) samples. Among the positive patients, there were 62% (n = 36) of female positive patients while in males, its ratio was 38% (n = 22). It was more common in the age between 30-50 years 55.17% (n = 32). It has shown the highest resistance towards Metronidazole 90% (n = 52), and the lowest toward Levofloxacin 65% (n = 38). Metronidazole resistance gene ( gene) was detected in (n = 13) isolates including (n = 9) isolates from females and (n = 4) from males. In the case of, the Clarithromycin resistance gene () (n = 10) was positive for including (n = 6) isolates from females and (n = 7) were positive for Amoxicillin ( gene) including (n = 2) in female and (n = 5) from male patients. CONCLUSION: This study highlights the increasing incidence of infections in both male and female patients. It also revealed the current status of antibiotic resistance and its resistance genes in patients facing gastrointestinal issues. Continuous surveillance of resistant clones will help in formulating strategies that can help in combating of resistant clone. It will also help clinician in proper prescription and management of infections.
Association between rs11362 and Caries Susceptibility in Permanent Dentition: A Cross Sectional Study.
Liu Q, Liu L, Chen S … +4 more , Yu X, Chen S, Cheng S, Zeng X
Discov Med · 2024 Sep · PMID 39327247 · Publisher ↗
BACKGROUND: Dental caries is a multifactorial chronic bacterial infectious disease. Variations in the predisposition of the general population to dental cavities suggest that genetic and immunological factors play signif...
BACKGROUND: Dental caries is a multifactorial chronic bacterial infectious disease. Variations in the predisposition of the general population to dental cavities suggest that genetic and immunological factors play significant roles in its pathogenesis. This study aims to explore the impact of the Beta-Defensin 1 () rs11362 polymorphism on caries susceptibility in permanent dentition among the Bai Kuyao and Zhuang ethnic groups in China. METHODS: A sample of 754 adolescents aged 12-15 was randomly selected from primary and junior high schools in Nandan County, Guangxi, China. All adolescents underwent clinical examinations, and DNA samples were collected. The genotype of rs11362 was determined using single nucleotide polymorphism (SNP) typing. The concentration of human β Defensin 1 (hBD-1) protein in saliva was measured using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The distribution of the rs11362 T allele was lower in the Bai Kuyao group compared to the Zhuang group. The disparity in the rs11362 genotype was statistically significant in the superficial dentin caries subgroup of the Bai Kuyao population ( = 0.017). Following adjustment for all potential confounding variables, the analysis revealed a heightened risk of superficial dental caries among CT genotype carriers in the Bai Kuyao population under a co-dominant model (odds ratios (OR) = 2.70; 95% confidence intervals (CI) [1.35-5.44]; = 0.005), and an increased risk among CC genotype carriers in the Bai Kuyao population under a dominant model (OR = 2.35; 95% CI [1.18-4.67]; = 0.015). A significant difference ( < 0.05) was noted in the distribution of rs11362 genotypes and salivary hBD-1 levels among the Bai Kuyao group. Salivary hBD-1 levels were notably higher in the CC genotype group (4.12 ± 2.07 ng/mL) compared to both the CT (2.77 ± 1.62 ng/mL) and TT genotype groups (2.32 ± 0.98 ng/mL). CONCLUSION: The rs11362 polymorphism showed an association with caries susceptibility in permanent teeth and influenced hBD-1 protein expression in saliva. Consequently, the polymorphism likely represents a concealed risk factor for caries.
Secretion of GPNMB from Neural Stem Cells Induced by ET-1 Contributes to Angiogenesis after Spinal Cord Injury.
Du Z, Wang B, He J … +1 more , Yu J
Discov Med · 2024 Sep · PMID 39327246 · Publisher ↗
BACKGROUND: The feeble plasticity of spinal cord microvascular endothelial cells (SCMECs) after trauma is one of the major causes of spinal cord injury (SCI). Neural stem cells (NSCs) play an important role in nerve repa...
BACKGROUND: The feeble plasticity of spinal cord microvascular endothelial cells (SCMECs) after trauma is one of the major causes of spinal cord injury (SCI). Neural stem cells (NSCs) play an important role in nerve repair. Glycoprotein nonmetastatic B (GPNMB) has neuroprotective effects and can be stimulated by endothelin 1 (ET-1), and its expression is upregulated in SCI. Here, we aim to investigate whether elevated ET-1 levels stimulate NSCs to secrete GPNMB, thereby further promoting angiogenesis. METHODS: Mouse SCMECs and NSCs were isolated, cultured, and identified by flow cytometry and immunofluorescence staining. NSCs were treated with ET-1, while SCMECs were cocultured with NSCs, followed by treatment with ET-1. NCS and SCMEC viability were evaluated using cell counting kit 8 (CCK-8) assay, while cell proliferation, migration, invasion, and angiogenesis were examined using 5'-Ethynyl-2'-Deoxyuridine (EdU) staining, wound healing assay, Transwell assay, and tube formation assay. GPNMB expression in NCSs and SCMECs was quantified by western blot assay, quantitative Real-Time polymerase chain reaction (qRT-PCR), or enzyme-linked immunosorbent assay (ELISA). RESULTS: Mouse SCMECs and NSCs were successfully isolated and cultured. ET-1 promoted NSC viability and proliferation and upregulated GPNMB expression. NSCs and ET-1-treated NSCs promoted the viability, migration, invasion, angiogenesis, and GPNMB expression in SCMECs compared with control group cells, while GPNMB antibody reversed the above effects of ET-1 on the SCMECs. CONCLUSION: ET-1 promotes SCMEC migration and invasion, along with angiogenesis, by enhancing NSC-mediated GPNMB secretion, so ET-1 may be a novel therapeutic target for SCI.
Regulates -Induced EMT Gene Transcription to Promote the Metastasis and Tumorigenesis of Papillary Thyroid Carcinoma.
Liu W, Lin R, Zhu C … +3 more , Chen Y, Gao Q, Zhong J
Discov Med · 2024 Sep · PMID 39327245 · Publisher ↗
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid, and its invasiveness and metastatic ability are closely related to patient prognosis. Chaperonin containing TCP1 subunit 2...
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid, and its invasiveness and metastatic ability are closely related to patient prognosis. Chaperonin containing TCP1 subunit 2 (CCT2) is an important component of the molecular chaperone protein complex and has been shown to regulate cell proliferation and migration in various tumors. Epithelial-mesenchymal transition (EMT) is a critical process in tumor metastasis, and Zinc Finger E-Box Binding Homeobox 1 () is a core transcription factor that regulates EMT. This study aims to explore how induces EMT gene transcription through , thereby promoting the metastasis and tumorigenesis of PTC. METHODS: CCT2 in PTC tissues was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. siRNA and overexpression vectors were used to silence and overexpress , respectively, and the effects on PTC cell migration, invasion, proliferation, and apoptosis were observed. Rescue experiments were used to investigate the effect of on and EMT-related genes. Cell apoptosis was detected by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay. Silencing was used to verify its effect on the oncogenic activity of . RESULTS: was found to be highly expressed in PTC tissues ( < 0.01). In and experiments, silencing inhibited the migration and invasion of PTC cells and their metastasis, while overexpression of produced the opposite effect. Additionally, promoted PTC cell proliferation and inhibited apoptosis ( < 0.01). Mechanistic studies revealed that upregulated expression ( < 0.01), thereby inducing EMT gene transcription ( < 0.01). Silencing reduced the oncogenic effect of . CONCLUSION: This study first revealed the high expression of in PTC and its essential role in the migration, invasion, proliferation, and anti-apoptosis of tumor cells. promotes the metastasis and tumorigenesis of PTC by regulating and EMT-related genes. These findings provide new potential targets for molecular targeted therapy of PTC and explore new directions for future clinical treatment strategies.
The Impact of Dibutyl Phthalate on Insulin Signaling in Human Skeletal Muscle Cells.
Shan D, Chen Y, Zhou K
Discov Med · 2024 Sep · PMID 39327244 · Publisher ↗
BACKGROUND: In China, the environmental concern of Dibutyl Phthalate (DBP) exposure significantly endangers human health by inducing insulin resistance (IR). Skeletal muscle tissue plays a critical role in this process....
BACKGROUND: In China, the environmental concern of Dibutyl Phthalate (DBP) exposure significantly endangers human health by inducing insulin resistance (IR). Skeletal muscle tissue plays a critical role in this process. However, the precise molecular mechanisms through which DBP interferes with the insulin signaling pathway remain to be fully elucidated. This study aims to explore the molecular mechanisms by which DBP induces IR in skeletal muscle, focusing on the phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT)-glucose transporter 4 (GLUT4) signaling pathway. METHODS: To investigate the molecular mechanisms underlying DBP-induced IR, an experimental study was established on a human skeletal muscle cell line (HSkMC). Expression levels of mRNA and proteins associated with key signaling genes within the insulin receptor (INSR)-insulin receptor substrate (IRS)-PI3K-AKT-GLUT4 pathway were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot techniques. Additionally, this study explored the effects of DBP alone and in combination with a PI3K inhibitor (BKM120) or phosphatase and tensin homolog (PTEN) overexpression lentivirus on these signaling components. RESULTS: Results from this study demonstrated that DBP exposure significantly decreased mRNA levels of , , , , and in HSkMC cells compared to untreated control cells. This reduction was exacerbated when DBP was combined with BKM120 or PTEN overexpression lentivirus, suggesting a synergistic effect. Furthermore, DBP treatment reduced the expression and phosphorylation of AKT2, indicating a disruption in the insulin signaling pathway. CONCLUSIONS: This study elucidates a molecular mechanism by which DBP induces IR in skeletal muscle cells, primarily through the deregulation of the PI3K-dependent insulin signaling pathway. These insights enhance comprehension of the pathophysiological changes associated with IR caused by environmental pollutants like DBP, potentially guiding future strategies for prevention and intervention.
PCGF2 Acts as an Oncogenic Driver in Colon Cancer through the Upregulation of CENPE.
Luo Q, Chen X, Tang J … +2 more , Yan W, Li Z
Discov Med · 2024 Sep · PMID 39327243 · Publisher ↗
BACKGROUND: Colon cancer (CC) is a highly prevalent malignancy that contributes significantly to global morbidity and mortality. The polycomb group ring finger 2 (PCGF2) has been identified as a relevant factor influenci...
BACKGROUND: Colon cancer (CC) is a highly prevalent malignancy that contributes significantly to global morbidity and mortality. The polycomb group ring finger 2 (PCGF2) has been identified as a relevant factor influencing the outcomes of CC. At the same time, the centromere-associated protein E (CENPE) is implicated in promoting carcinogenesis and adversely affecting the survival of tumor patients. The primary objective of this study was to elucidate the precise impact of PCGF2 on CC and unravel the underlying mechanisms associated with CENPE. METHODS: Human normal colon epithelial cells and CC cells were utilized to investigate the differential expression of PCGF2 and CENPE. CC cell line LOVO was exploited and transfected for PCGF2 regulation. Subsequently, cell viability and proliferation were assessed using the cell counting kit 8 (CCK-8) and colony forming assay. Cell viability and proliferation were assessed using the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, while cell migration and invasion capabilities were determined using the transwell assay, and mRNA levels of cell cycle-related genes were measured for evaluating cell cycle activation. In addition, mice were used for experiments to investigate the progression of CC cells with different levels of PCGF2. Moreover, GSK-923295 was used to inhibit CENPE, followed by the evaluation of cell progression. RESULTS: PCGF2 and CENPE were upregulated in CC cell lines ( < 0.001), and upregulation/downregulation of PCGF2 led to the upregulation and downregulation of CENPE ( < 0.001). The upregulation/downregulation of PCGF2 led to an increase/decrease in viability, proliferation, migration, and invasion while suppressing/enhancing apoptosis in LOVO cells ( < 0.001), promoting cell progression. The tumor progression of LOVO cells with PCGF2 knockdown was slower ( < 0.001). The PCGF2-promoting LOVO cell progression was disrupted when CENPE was inhibited, presented by the reversely decreased viability, proliferation, migration, invasion, and cell cycle activation, and increased apoptosis ( < 0.001). CONCLUSION: PCGF2 promotes CC cell progression by upregulating CENPE, providing PCGF2 inhibition and CENPE inhibition as potential therapeutic targets for treating CC.
NSAID-induced Gastric Ulcer Disease: A Deleterious Connection.
Islam H, Siddiqui A, Islam R … +6 more , Islam T, Ahmed S, Fahim M, Khalid M, Malik GMA, Imtiaz H
Discov Med · 2024 Sep · PMID 39327242 · Publisher ↗
Gastric ulcers induced by non-steroidal anti-inflammatory drug (NSAID) usage have become a common public health problem, and several studies have established chronic NSAID usage to be one of the risk factors for the path...
Gastric ulcers induced by non-steroidal anti-inflammatory drug (NSAID) usage have become a common public health problem, and several studies have established chronic NSAID usage to be one of the risk factors for the pathogenesis of peptic ulcers in patients. This review includes numerous articles that link NSAID usage with peptic mucosal erosion, especially among patients under anticoagulant therapy or with other risk factors. Risk factors for NSAID-induced peptic ulcers are reviewed, in addition to pathogenesis, clinical signs, symptoms, diagnosis, prevention, and treatments. We also emphasize effective methods for the prevention and management of peptic ulcers among NSAID users. Such methods include the use of selective Cyclo-oxygenase (COX-2) inhibitors as an alternative to aspirin or other Cyclo-oxygenase (COX-1) inhibitors, or using the lowest dosage possible in patients with other comorbidities. We have conducted a thorough review of the literature on diagnostic tests and alternative medication that can be used in the management of NSAID toxicity-induced ulcers.
Cytogenetics and the Revolution of Optical Genome Mapping in the Diagnosis of Diseases.
Al-Amer OM, Khubrani Y
Discov Med · 2024 Sep · PMID 39327241 · Publisher ↗
The study of chromosomal shape, characteristics, and behavior in somatic cell division (mitosis) during growth and development and in germ cell division (meiosis) during reproduction is known as cytogenetics. Many techni...
The study of chromosomal shape, characteristics, and behavior in somatic cell division (mitosis) during growth and development and in germ cell division (meiosis) during reproduction is known as cytogenetics. Many techniques can be used for cytogenetics, including fluorescent hybridization (FISH), spectral karyotyping (SKY), multicolor FISH (M-FISH), microarray, and optical genome mapping (OGM). OGM is a novel genome-wide method that can identify structural variants (SVs) and copy number variants (CNVs) with only one test. Genomic structural information that is difficult to obtain with DNA sequencing can be promptly obtained with OGM, in which large molecule lengths can be mapped at a reasonable cost. OGM is increasingly being used to investigate chromosome abnormalities in genetic disorders and human cancer, but it was first utilized in genome assembly and research. According to recent research, OGM is capable of identifying every clinically significant variation seen in trials using conventional care. OGM is being utilized to identify genomic abnormalities in patients with malignancies and constitutional illnesses. It is regarded as a revolution in the field of cytogenetics. Rather than sequencing DNA, OGM relies on DNA labeling. Currently, the OGM technique with the Saphyr system from Bionano Genomics is a widely utilized platform for cytogenetic analysis. In conclusion, OGM can now be considered a highly reliable method for the identification of chromosomal abnormalities in the diagnosis of tumors and hematological diseases.
Inflammaging, Epigenetic Damage, Mitochondrial Dysfunctions, and Macrophage Alterations are the Main Missing Pieces in the Complex Mosaic of Stem Cell Physiology.
Tatullo M, Rengo S, Sammartino G … +3 more , Simeone M, Valletta A, Gasparro R
Discov Med · 2024 Sep · PMID 39327240 · Publisher ↗
Aging is frequently associated with a progressive increase in chronic low-grade inflammation, known as "inflammaging". Numerous studies have shown that inflammaging is closely linked to the development of several age-rel...
Aging is frequently associated with a progressive increase in chronic low-grade inflammation, known as "inflammaging". Numerous studies have shown that inflammaging is closely linked to the development of several age-related diseases. However, the underlying mechanism and its causal role are still not fully understood despite this association. In the complex context of aging, mesenchymal stem cells (MSCs) undergo changes in behavior and functionality. This narrative topical review examines the recent advances in aging research, specifically focusing on the role of inflammaging and related mechanisms that contribute to age-related chronic diseases. The authors critically investigated whether and how inflammaging, epigenetic damage, mitochondrial changes, and macrophage alterations may influence stem cell behavior, highlighting the interplay between these factors and their potential therapeutic implications. By elucidating the mechanisms underlying these processes, we can gain valuable insights into the maintenance and regeneration of stem cell populations, providing the basis for novel therapeutic strategies targeting age-related decline and disease progression.
Current and Emerging Immunotherapies for Systemic AL Amyloidosis.
Moreno V, Saba L, Tama-Shekan S … +1 more , Chaulagain CP
Discov Med · 2024 Sep · PMID 39327239 · Publisher ↗
Systemic light-chain (AL) amyloidosis is a rare and complex clonal plasma cell neoplasm characterized by the production of misfolded and unstable immunoglobulin light-chains leading to multisystem amyloid deposition, whi...
Systemic light-chain (AL) amyloidosis is a rare and complex clonal plasma cell neoplasm characterized by the production of misfolded and unstable immunoglobulin light-chains leading to multisystem amyloid deposition, which progresses to organ dysfunction and eventual failure. The importance and urgency of AL amyloidosis depends on its potential to induce significant organ impairment, progressive course, risk of life-threatening complications, and the limited treatment options available. Treatment options and prognosis depend on the number and severity of organ involvement at the time of diagnosis with cardiac involvement carrying the worst outcomes. The treatments aim to target eliminating the underlying clonal plasma cell neoplasm and prevent the production and deposition of amyloid precursor immunoglobulin light-chain protein in the affected vital organs. Strategies for treating systemic AL amyloidosis have incorporated anti-plasma cell therapies approved in the management of multiple myeloma due to their shared cellular derivation. Quadruplet therapy of cyclophosphamide, bortezomib, dexamethasone and daratumumab (DaraCyborD) is the currently approved first-line induction therapy for systemic AL amyloidosis. Some patients need upfront autologous hematopoietic stem cell transplantation (HSCT) after high-dose melphalan conditioning particularly if DaraCyborD is not able to achieve complete hematologic response (CHR). Additionally, a promising treatment option involves disassembling amyloid deposits from the vital organs using monoclonal antibodies such as CAEL 101 or Birtamimab with the expectation of restoring damaged tissues of the vital organs affected thereby improving or reversing patients' symptoms. Both CAEL 101 and Birtamimab are currently being tested in phase 3 clinical trials for systemic AL amyloidosis patients with advanced cardiac involvement. This comprehensive review provides an up-to-date overview of AL amyloidosis therapy, with a particular focus on recent advances and future directions of immunotherapeutic strategies.
"" on a Recent Biologic (Ab-IPL-IL-17™) for IL-17-Mediated Diseases.
Saviano A, Mansour AA, Grieco P … +2 more , Iqbal AJ, Maione F
Discov Med · 2024 Aug · PMID 39190390 · Publisher ↗
Abstract loading — click title to view on PubMed.
Regulation of Nrf2/A20/eEF1A2 Axis by Ginsenoside Rb1: A Key Pathway in Alleviating Cerebral Ischemia-Reperfusion Injury.
He H, Yang Y, Zhang X … +2 more , Ying Y, Zheng B
Discov Med · 2024 Aug · PMID 39190389 · Publisher ↗
BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a prevalent neurological disorder, characterized by the oxidative stress and inflammatory response induced during the ischemia-reperfusion process, leading to si...
BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a prevalent neurological disorder, characterized by the oxidative stress and inflammatory response induced during the ischemia-reperfusion process, leading to significant damage to brain cells. Ginsenoside Rb1, a natural medicinal ingredient, possesses potential neuroprotective effects. This study aims to investigate the mechanism of action of ginsenoside Rb1 in CIRI and its protective effects on brain injury. METHODS: We utilized a mouse CIRI model and randomly divided the mice into control group, CIRI group, and ginsenoside Rb1 treatment group. The effects of Rb1 on brain tissue damage, apoptosis, expression of inflammatory factors, and pyroptotic cell numbers in CIRI mice were observed through triphenyl tetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, real-time reverse transcription polymerase chain reaction (qRT-PCR), and electron microscopy. In a cell model, the regulatory effect of Rb1 on oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell pyroptosis via the nuclear respiratoty factor 2/tumor necrosis factor-α (TNF-α)-induced Protein 3 (TNFAIP3, aka A20)/eukaryotic translation elongation factor 1A2 (Nrf2/A20/eEF1A2) axis was detected using Western blot and TUNEL staining. Additionally, the impact of Nrf2 inhibitor ML385 and eEF1A2 overexpression on the neuroprotective effect of Rb1 was assessed. Using the comprehensive experimental methods mentioned above, the neuroprotective mechanism of Rb1 in CIRI was thoroughly evaluated. RESULTS: Our findings demonstrate that treatment with ginsenoside Rb1 alleviated behavioral deficits induced by CIRI and reduced pathological damage in brain tissue. Furthermore, ginsenoside Rb1 treatment notably decreased oxidative stress and the inflammatory response induced by CIRI, leading to lower levels of inflammatory factors ( < 0.05). Further experimental results indicated that ginsenoside Rb1 promoted antioxidant and anti-inflammatory responses by regulating the activity of the Nrf2/A20/eEF1A2 axis. Additionally, ginsenoside Rb1 inhibited the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, thereby reducing the release of inflammatory factors and the occurrence of cell apoptosis. CONCLUSION: Our study results suggest that ginsenoside Rb1 exerts neuroprotective effects and alleviates brain injury induced by CIRI by regulating the Nrf2/A20/eEF1A2 axis and inhibiting the activation of the NLRP3 inflammasome. These findings provide new treatment insights for CIRI and support ginsenoside Rb1's development as a therapeutic drug. However, despite the promising nature of our findings, further research is required to validate these discoveries and explore the feasibility and safety of ginsenoside Rb1 in clinical applications. We hope that our study can provide new directions and strategies for the treatment and prevention of CIRI, contributing to the development of neuroprotective drugs.
Tumor Suppressor Inhibits the Progression of Cervical Cancer by Regulating the PTEN/Akt/mTOR Pathway.
Sun R, He SL, Liu HY … +2 more , Wang XW, Li SH
Discov Med · 2024 Aug · PMID 39190388 · Publisher ↗
OBJECTIVE: Cervical cancer (CC) ranks among the most prevalent malignant tumors affecting the female reproductive system. Nonetheless, various shortcomings exist within current treatment approaches for CC. Therefore, the...
OBJECTIVE: Cervical cancer (CC) ranks among the most prevalent malignant tumors affecting the female reproductive system. Nonetheless, various shortcomings exist within current treatment approaches for CC. Therefore, the quest for new intervention targets holds significant importance. Research has demonstrated that long non-coding RNA (lncRNA) long intergenic non-protein coding RNA 2487 () can suppress the development of oral squamous cell carcinoma (OSCC). However, its function and potential mechanisms in CC remain unclear, therefore, this study aims to investigate the role and potential mechanism of in CC. METHODS: and phosphatase and tensin homolog () expression were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) in CC tissue samples and constructed cell models. was either knocked down or overexpressed, and PTEN was knocked down in the CC (SiHa) cell line via transfection technology. The expression levels of and in SiHa cell lines were examined using RT-qPCR after various treatments. Cell proliferation ability was determined through Cell Counting Kit (CCK)-8 and colony formation assays, while the ability to invade and migrate was assessed via Transwell experiments. Western blot analysis was employed to measure the levels of key proteins in the PTEN/Akt/mechanistic target of the rapamycin (mTOR) signaling pathway. RESULTS: A positive correlation was observed between and , both of which were found to be downregulated in CC cells and tissues ( < 0.05). experiments demonstrated that overexpression of significantly inhibited colony formation ( < 0.01), invasion ( < 0.01), migration ( < 0.01), and proliferation ( < 0.01) of SiHa cells. Furthermore, overexpression led to upregulation of expression ( < 0.01) and inhibition of the Akt/mTOR signaling pathway ( < 0.01), while knockdown of produced the opposite effect ( < 0.01). Additionally, knocking down counteracted the inhibitory effects of overexpression on CC progression ( < 0.01) and the Akt/mTOR signaling pathway ( < 0.01). CONCLUSION: findings suggest that may impede the progression of CC by suppressing the Akt/mTOR signaling pathway through the upregulation of expression. Consequently, holds promise as a potential therapeutic target for the treatment of CC.
Simvastatin Inhibits the Formation of NETs by the Mac-1 Pathway to Reduce Hepatic Ischemia-Reperfusion Injury under High-Fat Conditions.
Wang S, Li Z, Chang Y … +3 more , Dong K, He D, Cheng X
Discov Med · 2024 Aug · PMID 39190387 · Publisher ↗
BACKGROUND: Hyperlipidemia is one of the main causes of aggravated hepatic ischemia-reperfusion injury (IRI). Simvastatin (SIM), a lipid-lowering drug, has been shown to effectively alleviate IRI caused by hyperlipidemia...
BACKGROUND: Hyperlipidemia is one of the main causes of aggravated hepatic ischemia-reperfusion injury (IRI). Simvastatin (SIM), a lipid-lowering drug, has been shown to effectively alleviate IRI caused by hyperlipidemia. However, the regulatory mechanism by which SIM alleviates hyperlipidemia-induced hepatic IRI is still not clear. This study aims to explore the potential mechanisms of SIM in inhibiting hyperlipidemia-induced hepatic IRI, providing new therapeutic strategies for the alleviation of hepatic IRI. METHODS: An animal model of hyperlipidemia was induced by feeding mice a high-fat diet for 8 weeks. Subsequently, a hepatic IRI animal model of hyperlipidemia was established by occluding the hepatic artery and portal vein for one hour, followed by reperfusion for 6 or 12 h. Enzyme linked immunosorbent assay, Western blotting, hematoxylin-eosin (H&E) staining, immunohistochemistry, immunofluorescence, and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling assay, were used to evaluate liver injury, neutrophil extracellular traps (NETs) formation, and related molecular mechanisms. RESULTS: Hepatic IRI was accelerated by hyperlipidemia, which enhanced the expression of oxidized low-density lipoprotein (oxLDL) and Macrophage-1antigen (Mac-1), leading to the promotion of NETs formation and apoptosis of liver cells. The administration of simvastatin reduced the levels of oxLDL and Mac-1, decreased the formation of NETs, and alleviated hepatic IRI induced by hyperlipidemia. CONCLUSIONS: Simvastatin reduced hyperlipidemia-induced hepatic IRI by inhibiting the formation of NETs through the regulation of the oxLDL/Mac-1 pathway.
Cystic Duct Exploration in Laparoscopic Cholecystectomy.
Zhang Y, Wang K, Li J
Discov Med · 2024 Aug · PMID 39190386 · Publisher ↗
BACKGROUND: Bile duct injury (BDI) is a severe complication following cholecystectomy and is therefore a particularly concerning surgical predicament for hepatobiliary surgeons. Owing to very high medical compensation aw...
BACKGROUND: Bile duct injury (BDI) is a severe complication following cholecystectomy and is therefore a particularly concerning surgical predicament for hepatobiliary surgeons. Owing to very high medical compensation awarded to patients suffering from BDI, surgeons need to exercise caution during surgery to avoid BDI. Herein, we explored a novel method to identify cystic duct during laparoscopic cholecystectomy (LC), expanding the applicability of this surgical approach. METHODS: Patients receiving LC between April 2021 and October 2022 at the Gaoyou People's Hospital were included in this retrospective clinical study and divided into two groups according to whether the cystic duct was incised (one group with LC alone, while another with laparoscopic cholecystectomy and cystic duct exploration [LCCDE]). Clinical and baseline characteristics of patients were collected, and the preoperative and postoperative biochemical parameters were compared. The surgical outcomes of LCCDE were observed. RESULTS: A total of 114 patients had undergone LC, while 162 patients had received LCCDE as treatment. There were no significant differences in age, gender, common bile duct diameter, preoperative and postoperative biochemical parameters between the two groups. No significant difference in the mean operation time between the LC and LCCDE groups was noted ( = 0.409). In the LCCDE group, white secretions in the cystic duct were observed in 92 patients (56.8%). CONCLUSIONS: The presence of intraoperative white secretions in the cystic duct may further confirm the presence of cystic duct, thereby enabling earlier detection of BDI. Importantly, LCCDE, as the new surgical method explored in this study, does not extend the operation time.
Pediatric Life Support in Prehospital Emergency Medicine: An Empirical Investigation in the Context of Taiwan's Critical Shortage of Pediatric Emergency Specialists.
Chen WF, Chan YK, Chang WH … +1 more , Hsieh MY
Discov Med · 2024 Aug · PMID 39190385 · Publisher ↗
BACKGROUND: This study aims to facilitate parental identification of designated emergency facilities for expeditious pediatric care within the framework of Taiwan's newly implemented "regional joint defense" approach to...
BACKGROUND: This study aims to facilitate parental identification of designated emergency facilities for expeditious pediatric care within the framework of Taiwan's newly implemented "regional joint defense" approach to pediatric emergency services. The research seeks to elucidate the mechanisms by which this novel system can enhance timely access to appropriate emergency care for children, potentially improving health outcomes and resource utilization in acute pediatric situations. METHODS: Factor analysis (FA) and triangular entropy matrix (TEM) analyzed the appearance, breathing and skin of pediatric assessment triangle (ABC of PAT), three types of prehospital pediatric emergence condition (PPEC), five levels of Taiwan's pediatric emergency triage (TPET), and applied the social learning theory (SLT) in educational doctrine, using experts' weighted questionnaires. RESULTS: Firstly, to address deficiencies in Taiwan's pediatric prehospital emergency medicine (PEM) system, integrating emergency medical knowledge (EMK) and pediatric life support (PLS) into medical education, staff training, and the national handbook for new parents is crucial. This equips parents to manage children's illnesses and prevent emergencies. Then, in life-threatening situations, immediate emergency room (ER) transport is vital for symptoms like whitish or purple lips, cold limbs, mottled skin, cold sweat, convulsions, dyspnea, chest dimples, weak consciousness, and oxygen saturation below 94%. Finally, for non-life-threatening emergencies, seek medical evaluation if symptoms include wheezing, chest tightness, chest pain, persistent high fever over 39 degrees with convulsions, chills, cold sweats, not eating or urinating for over 12 hours, or fever lasting more than 48 hours. CONCLUSION: Parents must remain calm and provide their baby with a sense of security while observing the development of physical symptoms. This approach enables them to effectively determine the most appropriate time to take their children to the emergency room, thereby avoiding life-threatening emergencies. Prompt and proper measures and treatments not only alleviate various discomforts caused by illness or medical emergencies but also reduce systemic distress, life-threatening situations, and unfortunate incidents before hospitalization.
Hypoxia-Induced Ephrin-B2 Facilitates Proliferation and Induces Glycolytic Metabolism in Cutaneous Squamous Cell Carcinoma by Modulating PKM2/HIF-1α Axis.
Wang X, Zhang Z, Hu G … +1 more , Zhou X
Discov Med · 2024 Aug · PMID 39190384 · Publisher ↗
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a fatal disease characterized by metabolic dysregulation. The role of ephrin type-B receptor 2 (ephrin-B2), a crucial molecule in cancer cell biology, in regulating...
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a fatal disease characterized by metabolic dysregulation. The role of ephrin type-B receptor 2 (ephrin-B2), a crucial molecule in cancer cell biology, in regulating glycolysis and cell proliferation of cSCC is not well understood. This study aimed to investigate the biological pathways by which ephrin-B2 impacts the glycolysis and cell proliferation of cSCC. METHODS: Ephrin-B2 expression levels in cSCC were determined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting. expression in cSCC cells was manipulated using overexpression and knockdown approaches. A series of assays, such as cell counting kit-8 (CCK-8), Transwell assay, immunofluorescence assay, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, and Western blotting, were employed to delineate the biological roles of ephrin-B2/pyruvate kinase muscle isoenzyme 2 (PKM2)/hypoxia-inducible factor 1 alpha (HIF-1α) in proliferation, migration, invasion, and glucose metabolism of cSCC. RESULTS: This study highlights an upregulation of expression in cSCC. Knockdown of significantly suppressed the proliferation, migration, invasion, and glucose metabolism of cSCC cells. Moreover, expression was upregulated under hypoxic conditions. At the molecular level, knockdown resulted in the downregulation of and expression. Additionally, the overexpression of or successfully rescued the diminished proliferation, migration, invasion and glucose metabolism induced by knockdown in cSCC cells. CONCLUSION: These findings suggest that ephrin-B2 suppression may hinder cSCC cell proliferation and glycolytic metabolism, potentially via the PKM2/HIF-1α axis modulation.
Targeting STIM1 Contributes to Alleviating Remodeling of Vascular Smooth Muscle Cells in Atherosclerosis.
Cui Z, Zhang Y, Sheng L
Discov Med · 2024 Aug · PMID 39190383 · Publisher ↗
BACKGROUND: Remodeling of vascular smooth muscle cells (VSMCs), as a pathological hallmark of cardiovascular diseases, is related to the molecular rewiring of Calcium signaling, which induces upregulation of stromal inte...
BACKGROUND: Remodeling of vascular smooth muscle cells (VSMCs), as a pathological hallmark of cardiovascular diseases, is related to the molecular rewiring of Calcium signaling, which induces upregulation of stromal interaction molecule (STIM) proteins. This study analyzed the influence of STIM1 proteins on the remodeling of VSMCs in atherosclerosis (AS). METHODS: After oxidized low-density lipoprotein (ox-LDL) treatment and transfection, VSMC viability, migration, and invasion were separately measured using Cell Counting Kit-8, Scratch assay, and Transwell assay. An animal AS model was constructed, and histological analysis via hematoxylin-eosin staining was conducted on the aorta. RESULTS: Ox-LDL promoted expression of STIM1 and Orai calcium release-activated calcium modulator 1 (Orai1). STIM1 or Orai1 downregulation suppressed viability, migration, invasion, and phenotypic switching of ox-LDL-treated VSMCs, whereas STIM1 or Orai1 upregulation had opposite effects. Orai1 level was upregulated by STIM1 overexpression. Orai1 silencing reversed the effects of STIM1 overexpression in VSMCs. STIM1 deficiency alleviated AS and regulated expression of Orai1 and phenotypic switch-related factors . CONCLUSION: STIM1 deficiency suppresses viability, migration, invasion, and phenotypic switching of ox-LDL-induced VSMCs and alleviates AS by inhibiting Orai1.
Clinical Analysis of Abnormal Brainstem Auditory Evoked Potential in Neonates with Hyperbilirubinemia.
Xu J, Shu D, Li Q … +4 more , Wang Y, Gu F, Zhao X, Lu L
Discov Med · 2024 Aug · PMID 39190382 · Publisher ↗
BACKGROUND: Severe neonatal hyperbilirubinemia can cause hearing impairment. Bilirubin can be deposited in nerve cells, and the brainstem and the 8th nerve are especially sensitive to bilirubin toxicity. Abnormal changes...
BACKGROUND: Severe neonatal hyperbilirubinemia can cause hearing impairment. Bilirubin can be deposited in nerve cells, and the brainstem and the 8th nerve are especially sensitive to bilirubin toxicity. Abnormal changes in brainstem auditory evoked potential (BAEP) can be observed, and the BAEP test measures a nerve potential induced by short, high-frequency sound stimulation; thus, it is able to detect damage to the auditory conduction pathway in children. We aimed to identify relationships between clinical features and BAEP abnormalities in children with hyperbilirubinemia and to assess the predictive power of these risk factors for bilirubin-induced neurological damage. METHODS: Children with hyperbilirubinemia were evaluated with BAEP and retrospectively enrolled in the study between January 2012 and December 2018. Multivariate logistic regression was performed to identify independent predictors of BAEP abnormalities. RESULTS: Of the 561 children with hyperbilirubinemia enrolled, the BAEP anomaly group accounted for 198 (35.3%) cases. Except for body weight, there were no significant differences in the general data between the two groups with hyperbilirubinemia ( > 0.05). Univariate analysis showed that prematurity, abnormal umbilical cord, and gestational diabetes during pregnancy were significantly correlated with abnormal BAEP. Multivariate logistic regression analysis identified prematurity ( = 0.001), gestational diabetes ( = 0.03), Premature rupture of membranes ( = 0.013), total serum bilirubin (TSB), bilirubin/albumin (B/A) as independent risk factors for BAEP abnormalities. The prediction accuracy of TSB (Area Under Curve (AUC) = 0.557) and B/A (AUC = 0.566) was low, indicating that abnormal BAEP should be detected by multiple factors. CONCLUSIONS: Multivariate detection is beneficial for predicting the occurrence of auditory nerve injury in patients with hyperbilirubinemia.
PAR1 Activation, via LMBR1/BMP Axis, Promotes the Osteogenesis of Periodontal Ligament Stem Cells (PDLSCs) and Alleviates the Inhibitory Effect of Sodium Butyrate on PDLSCs Osteogenesis.
Xia L, Yang Z, Hu C
Discov Med · 2024 Aug · PMID 39190381 · Publisher ↗
BACKGROUND: Periodontitis is the leading cause of tooth loss and can exacerbate various systemic inflammatory conditions. Periodontal ligament stem cells (PDLSCs) stand out as prominent and favorable candidates for promo...
BACKGROUND: Periodontitis is the leading cause of tooth loss and can exacerbate various systemic inflammatory conditions. Periodontal ligament stem cells (PDLSCs) stand out as prominent and favorable candidates for promoting periodontal tissue regeneration. This study aimed to investigate whether the protease-activated receptor type 1 (PAR1) can mitigate the sodium butyrate (NaB)-induced PDLSCs osteogenesis inhibition and unravel the underlying mechanism. METHODS: Public datasets from the Gene Expression Omnibus (GEO) were utilized to analyze differentially expressed genes (DEGs) in periodontitis and subsequent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. PDLSCs were cultured normally in control medium (CM) as the negative control or in osteogenic medium (OM) to induce osteogenesis. PAR1 was either activated or suppressed using a selective agonist or antagonist (OM+agonist and OM+antagonist). The evaluation of PDLSCs osteogenesis was based on the levels of osteogenesis-related markers, including runt-related transcription factor 2 (RUNX2), osterix (OSX), osteocalcin (OCN), and osteopontin (OPN), alkaline phosphatase (ALP) activity, and calcium concentration. Additionally, cell proliferation and osteogenic differentiation were measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Alizarin Red Staining. To determine the PAR1 targeting the limb development membrane protein 1 (LMBR1)/bone morphogenetic protein (BMP) pathway, LMBR1 was upregulated through cell transfection and BMP2 was inhibited using the selective inhibitor Noggin protein. Finally, NaB was introduced into PDLSCs to investigate the effect on NaB-induced inhibition of PDLSCs osteogenesis. RESULTS: PAR1, RUNX2, OSX, OCN, OPN, proliferation, ALP activity, calcium concentration, osteogenic differentiation, BMP2, and BMP4 exhibited significant increases in PDLSCs cultured in OM ( < 0.01). These parameters were further elevated by PAR1 agonist and conversely reduced by PAR1 antagonist ( < 0.01). Conversely, LMBR1 was decreased in PDLSCs cultured in OM ( < 0.001), with further reduction induced by PAR1 agonist and a reverse increase observed with PAR1 antagonist ( < 0.001). OE-LMBR1 transfection successfully elevated LMBR1 levels, subsequently inhibiting BMP2 and BMP4 ( < 0.001). Meanwhile, the Noggin protein effectively suppressed BMP2 and BMP4 ( < 0.001). All observed osteogenesis-related changes were reversed by the increased LMBR1 or inhibition of the BMP pathway ( < 0.001). Furthermore, NaB suppressed osteogenesis-related changes in OM-cultured PDLSCs ( < 0.001), and these effects were entirely reversed by PAR1 agonist ( < 0.001). Conversely, the increased LMBR1 or inhibited BMP pathway disrupted the osteogenesis reversion induced by PAR1 agonist ( < 0.001). CONCLUSION: The activation of PAR1, through suppressing LMBR1 signaling and activating BMP pathway, demonstrates the ability to enhance the osteogenesis of PDLSCs and mitigate the inhibitory effects on PDLSCs osteogenesis caused by NaB.
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