Braz. J. Med. Biol. Res. [JOURNAL]
Sun
200 papers
Neurocognitive effects of proanthocyanidin in Alzheimer's disease: a systematic review of preclinical evidence.
Reshma A, Subramanian A, Kumarasamy V … +7 more , Tamilanban T, Sekar M, Gan SH, Subramaniyan V, Wong LS, Rani NNIM, Wu YS
Braz J Med Biol Res · 2024 · PMID 39504064 · Full text
Cognitive disorders and dementia largely influence individual independence and orientation. Based on the Alzheimer's Disease International (ADI) estimation, approximately 75% of individuals with dementia are undiagnosed....
Cognitive disorders and dementia largely influence individual independence and orientation. Based on the Alzheimer's Disease International (ADI) estimation, approximately 75% of individuals with dementia are undiagnosed. In fact, in some low- and middle-income countries, the percentage is as high as 90%. In this systematic review, which is based on PRISMA guidelines, we aim to identify the mechanism of action of proanthocyanidin. Finding a natural product alternative as a potential nootropic can help increase the number of armamentariums against dementia and other cognitive impairments. In this preclinical research, we determined the effect of proanthocyanidins on Alzheimer's disease (AD) by searching electronic bibliographic databases like Scopus, Proquest, ScienceDirect, PubMed, and Google. There was no imposed time limit. However, the search was limited to only English articles. The review protocol is registered on PROSPERO as CRD42022356301. A population, intervention, control, and outcomes (PICO) technique was utilized for report inclusion, and all reports were assessed for risk of bias by using the SYRCLE's RoB tool. The article's bibliographic information, induction model, type of proanthocyanidins, animal strain/weight/age, and outcome measurements were acquired from ten papers and are reported here. Further analysis was validated and determined for the review. The included studies met the review's inclusion criteria and suggested that proanthocyanidins have a neurocognitive effect against AD. Additionally, the effectiveness of proanthocyanidins in reducing oxidative stress, acetylcholinesterase activity, amyloid beta, its efficacy in alleviating superoxide dismutase, cognitive properties, and in facilitating cholinergic transmission in various models of AD has been collectively observed in ten studies.
Analysis of the differences in immune-related genes and immune cell subtypes in acute myocardial infarction.
Li Z, Kang L, Jiang K
Braz J Med Biol Res · 2024 · PMID 39417451 · Full text
Acute myocardial infarction (AMI) continues to be a leading cause of death globally, with distinct immune cell dynamics in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarc...
Acute myocardial infarction (AMI) continues to be a leading cause of death globally, with distinct immune cell dynamics in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) playing a critical role in disease progression and patient outcomes. Sample data for STEMI and NSTEMI were downloaded from the Sequence Read Archive (SRA) database (https://www.ncbi.nlm.nih.gov/sra). Differences and correlations of immune infiltrating cells were assessed by CIBERSORT. Differentially expressed genes (DEGs) were identified between STEMI and NSTEMI, followed by functional analysis. Immune-related DEGs were further identified. Some immune-related DEGs were selected to perform expression verification using real-time PCR. There was a significant difference in immune cells between STEMI and NSTEMI, including activated dendritic cells, memory CD4 T cells, mast cells, and CD8 T cells. A total of 229 DEGs were identified, with functions related to inflammatory regulation and drug metabolism. A total of 21 immune-related DEGs, which may play important roles in STEMI and NSTEMI, were identified. Among the 21 immune-related DEGs, genes like CCL18, NRP2, CXCR2, CXCL9, KIR2DL4, BPIFB1, and IL33 were significantly correlated with immune cells and had a tendency for differential expression between STEMI and NSTEMI patients. Our study reveals differences in the distribution of immune cell subsets between STEMI and NSTEMI, highlighting key immune-related genes and their association with immune cells, which may provide new insights into the treatment of AMI.
Across-surface distances after one- and two-stage palatoplasty in children with oral cleft.
Ambrosio ECP, Bergamo MTOP, Sforza C … +3 more , Carrara CFC, Machado MAAM, Oliveira TM
Braz J Med Biol Res · 2024 · PMID 39417450 · Full text
The goal of this study was to digitally evaluate the development of maxillary dental arches of children with unilateral cleft lip and palate treated with one- and two-stage palatal closure. One hundred and sixty-eight di...
The goal of this study was to digitally evaluate the development of maxillary dental arches of children with unilateral cleft lip and palate treated with one- and two-stage palatal closure. One hundred and sixty-eight digitized dental models of cheiloplasty and one-stage palatoplasty (G1) and cheiloplasty and two-stage palatoplasty (G2) were evaluated at preoperative time 1 (T1), preoperative time 2 (T2), and postoperative (T3). The following surface distances were evaluated: across surface distance; cleft widths anterior (P-P') and posterior (U-U') cleft widths, intercanine width (C-C'), and intertuberosity width (T-T'); smallest (P'-T') and largest (P-T) segment lengths; and smallest (C'-D') and largest (C-D) segment cleft depths. In G1, P-P', U-U', and C-C' reduced at T2, unlike P'-T' (P<0.05). P-T and C'-D' distances increased at T3 (P<0.05), while C-D increased at all stages (P<0.001). In G2, U-U' and C-C' reduced at T2 (P<0.05), while P'-T', P-T, C'-D', and C-D' increased at T3 (P<0.001). In an intergroup analysis of growth rate, G2 showed higher growth percentages compared to G1, in which C'-D' was significant (P=0.038). Furthermore, C'-D' presented a coefficient of determination of 0.076 (P=0.039). In conclusion, dental arch development is influenced by the rehabilitation protocol. However, in the sample evaluated, the comparison suggested that individuals whose palate was operated on in two stages had the most favorable palatal growth.
CAR-T therapy for gastrointestinal cancers: current status, challenges, and future directions.
Li W, Huang Y, Zhou X … +3 more , Cheng B, Wang H, Wang Y
Braz J Med Biol Res · 2024 · PMID 39417449 · Full text
Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary immunotherapeutic strategy that has shown efficacy in hematological malignancies. However, its application in solid tumors, particularly gastrointestinal...
Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary immunotherapeutic strategy that has shown efficacy in hematological malignancies. However, its application in solid tumors, particularly gastrointestinal cancers, faces significant challenges. These include the selection of target antigens, the complexity of the tumor microenvironment, and safety and toxicity concerns. This review provides a current overview of CAR-T therapy in various gastrointestinal cancers, such as esophageal, gastric, colorectal, pancreatic, and liver cancers. It discusses the limitations and future directions of CAR-T therapy in this context. This review highlights innovative strategies, including novel target antigens, multispecific CAR-T cells, armored CAR-T cells, and the development of universal CAR-T cells. These insights aim to inform ongoing research and foster advancements in CAR-T therapy for gastrointestinal cancers.
Mesenchymal stem cells from different sources for sepsis treatment: prospects and limitations.
Chen H, Ling X, Zhao B … +4 more , Chen J, Sun X, Yang J, Li P
Braz J Med Biol Res · 2024 · PMID 39417448 · Full text
Sepsis is a systemic inflammatory response syndrome in which the host response to infection is dysregulated, leading to circulatory dysfunction and multi-organ damage. It has a high mortality rate and its incidence is in...
Sepsis is a systemic inflammatory response syndrome in which the host response to infection is dysregulated, leading to circulatory dysfunction and multi-organ damage. It has a high mortality rate and its incidence is increasing year by year, posing a serious threat to human life and health. Mesenchymal stem cells (MSC) have the following properties: hematopoietic support, provision of nutrients, activation of endogenous stem/progenitor cells, repair of tissue damage, elimination of inflammation, immunomodulation, promotion of neovascularization, chemotaxis and migration, anti-apoptosis, anti-oxidation, anti-fibrosis, homing, and many other effects. A large number of studies have confirmed that MSC from different sources have their own characteristics. This article reviews the pathogenesis of sepsis, the biological properties of MSC, and the advantages and disadvantages of different sources of MSC for the treatment of sepsis and their characteristics.
Multipotent mesenchymal stromal/stem cell-based therapies for acute respiratory distress syndrome: current progress, challenges, and future frontiers.
Sababathy M, Ramanathan G, Ganesan S … +6 more , Sababathy S, Yasmin AR, Ramasamy R, Foo JB, Looi QH, Nur-Fazila SH
Braz J Med Biol Res · 2024 · PMID 39417447 · Full text
Acute respiratory distress syndrome (ARDS) is a critical, life-threatening condition marked by severe inflammation and impaired lung function. Mesenchymal stromal/stem cells (MSCs) present a promising therapeutic avenue...
Acute respiratory distress syndrome (ARDS) is a critical, life-threatening condition marked by severe inflammation and impaired lung function. Mesenchymal stromal/stem cells (MSCs) present a promising therapeutic avenue due to their immunomodulatory, anti-inflammatory, and regenerative capabilities. This review comprehensively evaluates MSC-based strategies for ARDS treatment, including direct administration, tissue engineering, extracellular vesicles (EVs), nanoparticles, natural products, artificial intelligence (AI), gene modification, and MSC preconditioning. Direct MSC administration has demonstrated therapeutic potential but necessitates optimization to overcome challenges related to effective cell delivery, homing, and integration into damaged lung tissue. Tissue engineering methods, such as 3D-printed scaffolds and MSC sheets, enhance MSC survival and functionality within lung tissue. EVs and MSC-derived nanoparticles offer scalable and safer alternatives to cell-based therapies. Likewise, natural products and bioactive compounds derived from plants can augment MSC function and resilience, offering complementary strategies to enhance therapeutic outcomes. In addition, AI technologies could aid in optimizing MSC delivery and dosing, and gene editing tools like CRISPR/Cas9 allow precise modification of MSCs to enhance their therapeutic properties and target specific ARDS mechanisms. Preconditioning MSCs with hypoxia, growth factors, or pharmacological agents further enhances their therapeutic potential. While MSC therapies hold significant promise for ARDS, extensive research and clinical trials are essential to determine optimal protocols and ensure long-term safety and effectiveness.
Efficacy of convalescent plasma in hospitalized COVID-19 patients: findings from a controlled trial.
Costa TP, Aoki M, Ribeiro CM … +4 more , Socca E, Itinose L, Basso R, Blanes L
Braz J Med Biol Res · 2024 · PMID 39383382 · Full text
The COVID-19 pandemic has driven the search for alternative therapies, including convalescent plasma, historically used in infectious diseases. Despite results in other diseases, its effectiveness against COVID-19 remain...
The COVID-19 pandemic has driven the search for alternative therapies, including convalescent plasma, historically used in infectious diseases. Despite results in other diseases, its effectiveness against COVID-19 remains uncertain with conflicting results in clinical trials. A pragmatic, single-center, prospective, and open randomized controlled trial was carried out in a hospital in Brazil, with the aim of evaluating the impact of convalescent plasma on the clinical improvement of patients hospitalized with COVID-19. The World Health Organization (WHO) ordinal scale was used to measure clinical improvement, focusing on the reduction in disease severity by up to 2 points, while antibody and C-reactive protein levels were monitored over time. After hospital admission, participants were randomized 1:1 to receive convalescent plasma and standard treatment or to be part of the control group with standard treatment. Follow-up was carried out on days 1, 3, 7, 14 and/or at discharge. From January 14 to April 4, 2022, 38 patients were included, but 3 were excluded due to protocol deviations, resulting in a total of 35 patients: 19 in the control group and 16 in the plasma group. There was no significant difference in clinical improvement between the convalescent plasma group and the control group, nor in secondary outcomes. The study had limitations due to the small number of patients and limited representation of COVID-19 cases. Broader investigations are needed to integrate therapies into medical protocols, both for COVID-19 and other diseases. Conducting randomized studies is challenging due to the complexity of medical conditions and the variety of treatments available.
Osteogenic mechanism of deciduous teeth periodontal ligament stem cells in inflammatory environment.
Li JY, Dai SS, Li ZY … +2 more , Guo QY, Liu F
Braz J Med Biol Res · 2024 · PMID 39383381 · Full text
This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth per...
This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 μg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 μg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 μg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.
Potential biomarkers as a predictive factor of response to primary chemotherapy in breast cancer patients.
Buono FO, Pugliese RDS, Silveira WAD … +5 more , Tirapelli DPC, Reis FJCD, Andrade JM, Carrara HHA, Tiezzi DG
Braz J Med Biol Res · 2024 · PMID 39383380 · Full text
In this study, we identified miRNAs and their potential mRNA targets that are intricately linked to primary chemotherapy response in patients with invasive ductal carcinomas. A cohort of individuals diagnosed with advanc...
In this study, we identified miRNAs and their potential mRNA targets that are intricately linked to primary chemotherapy response in patients with invasive ductal carcinomas. A cohort of individuals diagnosed with advanced invasive breast ductal carcinoma who underwent primary chemotherapy served as the cornerstone of our study. We conducted a comparative analysis of microRNA expression among patients who either responded or did not respond to primary systemic therapy. To analyze the correlation between the expression of the whole transcriptome and the 24 differentially expressed (DE) miRNAs, we harnessed the extensive repository of The Cancer Genome Atlas (TCGA) database. We mapped molecular mechanisms associated with these miRNAs and their targets from TCGA breast carcinomas. The resultant expression profile of the 24 DE miRNAs emerged as a potent and promising predictive model, offering insights into the intricate dynamics of chemotherapy responsiveness of advanced breast tumors. The discriminative analysis based on the principal component analysis identified the most representative miRNAs across breast cancer samples (miR-210, miR-197, miR-328, miR-519a, and miR-628). Moreover, the consensus clustering generated four possible clusters of TCGA patients. Further studies should be conducted to advance these findings.
Synergistic effect of venetoclax and ibrutinib on ibrutinib-resistant ABC-type DLBCL cells.
Jin F, He L, Chen Y … +6 more , Tian W, Liu L, Ge L, Qian W, Xia L, Yang M
Braz J Med Biol Res · 2024 · PMID 39383379 · Full text
Despite the widespread use of R-CHOP therapy in diffuse large B-cell lymphoma (DLBCL), the therapeutic efficacy for this disease remains suboptimal, primarily due to the heterogeneity of refractory and/or relapsed diseas...
Despite the widespread use of R-CHOP therapy in diffuse large B-cell lymphoma (DLBCL), the therapeutic efficacy for this disease remains suboptimal, primarily due to the heterogeneity of refractory and/or relapsed diseases. To address this challenge, optimization of DLBCL treatment regimens has focused on the strategy of combining an additional drug "X" with R-CHOP to enhance efficacy. However, the failure of R-CHOP combined with the BTK inhibitor ibrutinib in treating ABC-type DLBCL patients has raised significant concerns regarding ibrutinib resistance. While some studies suggest that venetoclax may synergize with ibrutinib to kill ibrutinib-resistant cells, the underlying mechanisms remain unclear. Our study aimed to validate the enhanced tumor-suppressive effect of combining ibrutinib with venetoclax against ibrutinib-resistant cells and elucidate its potential mechanisms. Our experimental results demonstrated that ibrutinib-resistant cells exhibited significant cytotoxicity to the combination therapy of ibrutinib and venetoclax, inducing cell apoptosis through activation of the mitochondrial pathway and inhibition of aerobic respiration. Furthermore, we validated the inhibitory effect of this combination therapy on tumor growth in in vivo models. Therefore, our study proposes that the combination therapy of ibrutinib and venetoclax is a promising treatment strategy that can be applied in clinical practice for ABC-type DLBCL, offering a new solution to overcome the urgent challenge of ibrutinib resistance.
Circulating JKAP levels may correlate with postpartum anxiety and depression through its interaction with T helper 17 cells.
Zhang J, Li C, Chen Z … +4 more , Zhao X, He Y, Wei L, Kong N
Braz J Med Biol Res · 2024 · PMID 39383378 · Full text
Jun N-terminal kinase pathway-associated phosphatase (JKAP) regulates CD4+ T-cell differentiation and immunity, which are linked to mental disorders. This study aimed to explore the relationships between JKAP and T helpe...
Jun N-terminal kinase pathway-associated phosphatase (JKAP) regulates CD4+ T-cell differentiation and immunity, which are linked to mental disorders. This study aimed to explore the relationships between JKAP and T helper 17 (Th17)/regulatory T (Treg) ratio, as well as their associations with anxiety and depression in postpartum women. Serum JKAP were measured by enzyme-linked immunosorbent assay and blood Th17 and Treg cells were measured by flow cytometry in 250 postpartum women. Anxiety and depression were evaluated by the 6-item State-Trait Anxiety Inventory (STAI6) and Edinburgh Postnatal Depression Scale (EPDS). Anxiety and depression rates were 22.0 and 28.4%, respectively, among postpartum women. Notably, JKAP was negatively associated with the STAI6 (P=0.002) and EPDS scores (P<0.001) in postpartum women and was lower in postpartum women with anxiety (P=0.023) or depression (P=0.002) than in those without. Moreover, JKAP was inversely related to Th17 cells and Th17/Treg ratio but positively correlated with Treg cells in postpartum women (all P<0.001). Interestingly, Th17 cells and Th17/Treg ratio were both positively associated with STAI6 and EPDS scores in postpartum women (all P<0.001). Furthermore, Th17 cells and Th17/Treg ratio were lower in postpartum women with anxiety or depression than in those without (all P<0.01). Nevertheless, Treg cells were not linked to anxiety or depression in postpartum women. JKAP was negatively associated with Th17 cells and Th17/Treg ratio; moreover, they all related to anxiety and depression in postpartum women, indicating that JKAP may be involved in postpartum anxiety and depression via interactions with Th17 cells.
Amelioration of nephrotoxicity by targeting ferroptosis: role of NCOA4, IREB2, and SLC7a11 signaling.
Sharawy N, Aboulhoda BE, Khalifa MM … +5 more , Morcos GN, Morsy SAAG, Alghamdi MA, Khalifa IM, Abd Algaleel WA
Braz J Med Biol Res · 2024 · PMID 39383377 · Full text
Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms...
Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms that disrupt iron homeostasis and lead to ferroptosis are yet to be elucidated. In this study, we aimed to investigate the involvement of nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor that mediates ferroptosis and autophagic degradation of ferritin in nephrotoxicity. Adult male Sprague-Dawley rats were randomly-assigned to four groups: control group, cisplatin (Cis)-treated group, deferiprone (DEF)-treated group, and Cis+DEF co-treated group. Serum, urine, and kidneys were isolated to perform biochemical, morphometric, and immunohistochemical analysis. Iron accumulation was found to predispose to ferroptotic damage of the renal tubular cells. Treatment with deferiprone highlights the role of ferroptosis in nephrotoxicity. Upregulation of NCOA4 in parallel with low ferritin level in renal tissue seems to participate in iron-induced ferroptosis. This study indicated that ferroptosis may participate in cisplatin-induced tubular cell death and nephrotoxicity through iron-mediated lipid peroxidation. Iron dyshomeostasis could be attributed to NCOA4-mediated ferritin degradation.
NLRP1 inhibits lung adenocarcinoma growth through mediating mitochondrial dysregulation in an inflammasome-independent manner.
Lin CJ, Tian GA, Zhao WY … +4 more , Tian Y, Liu YR, Gu DN, Tian L
Braz J Med Biol Res · 2024 · PMID 39258674 · Full text
NLRP1, the first identified inflammasome-forming sensor, is thought to be involved in cancer, yet its definite function in lung adenocarcinoma (LUAD) remains unclear. Herein, we explored the expression and function of NL...
NLRP1, the first identified inflammasome-forming sensor, is thought to be involved in cancer, yet its definite function in lung adenocarcinoma (LUAD) remains unclear. Herein, we explored the expression and function of NLRP1 in LUAD. Decreased NLRP1 expression was identified in LUAD, which was associated with a poor prognosis. Overexpression of NLRP1 inhibited tumor growth in vitro and in vivo. Mechanically, this effect was observed regardless of inflammasome activation. Further studies revealed that overexpression of NLRP1 downregulated the phosphorylation of DRP1 and promoted mitochondrial fusion, which was mediated by inhibition of NF-κB activity. NF-κB agonist could neutralize the effect of NLRP1 on mitochondrial dynamics. In addition, LUAD sensitivity to cisplatin was enhanced by decreased mitochondrial fission resulting from up-regulated NLRP1. In conclusion, our findings demonstrated an unexpected role of NLRP1 in LUAD by modulating mitochondrial activities, which provides strong evidence for its potential in LUAD treatment.
Plasma cytokine levels as markers of pathogenesis and treatment response in patients with non-tuberculous mycobacterial pulmonary disease.
Zhao S, Zhang Z, Xu J … +4 more , Zhou Z, Wu Y, Wu Y, Jiang G
Braz J Med Biol Res · 2024 · PMID 39258673 · Full text
We investigated the value of plasma cytokine levels as markers of pathogenesis and treatment response in patients with non-tuberculous mycobacteria (NTM) pulmonary disease. Plasma cytokine levels were measured and compar...
We investigated the value of plasma cytokine levels as markers of pathogenesis and treatment response in patients with non-tuberculous mycobacteria (NTM) pulmonary disease. Plasma cytokine levels were measured and compared among patients with NTM pulmonary disease (n=111), tuberculosis (TB) patients (n=50), and healthy individuals (n=40). Changes during treatment were monitored at 3 and 6 months after treatment. According to the treatment response, NTM patients were classified as 'resistance' or 'sensitivity' responders. The results revealed that five out of twelve cytokines exhibited significantly higher levels in NTM patients compared to controls. Among these, interleukin (IL)-6 demonstrated the strongest discriminating capacity for NTM. Furthermore, when combined with IL-1β, they efficiently distinguished between NTM drug-resistant and drug-sensitive patients, as well as between NTM and TB groups. Additionally, IL-6 levels initially rose and then decreased in the NTM drug-resistant group during the six months of treatment, similar to the behavior of IL-1β in the NTM drug-sensitive group. Subgroup analyses of the sensitive group with differential treatment responses revealed an increase in IL-10 levels in the six-month treatment responders. A high IL-6/IL-10 ratio was associated with increased disease severity of NTM and TB. Collectively, combinations of various plasma cytokines, specifically IL-1β, IL-6, and IL-10, effectively distinguished NTM patients with varying mycobacterial burdens, with IL-6 and IL-10 emerging as potential biomarkers for early treatment response. The combination of IL-6 and IL-1β demonstrated the highest discriminatory value for distinguishing between NTM-resistant and NTM-sensitive groups as well as between NTM and TB groups.
Cognitive behavioral stress management effectively facilitates neurologic recovery, alleviates mental distress, and elevates health status in acute ischemic stroke patients.
Yue S, Yin Y, Liu J … +1 more , Liu Z
Braz J Med Biol Res · 2024 · PMID 39258672 · Full text
Cognitive behavioral stress management (CBSM) relieves physical and psychological burdens in patients with some central nervous system diseases, while its utility in acute ischemic stroke (AIS) patients is unclear. This...
Cognitive behavioral stress management (CBSM) relieves physical and psychological burdens in patients with some central nervous system diseases, while its utility in acute ischemic stroke (AIS) patients is unclear. This study aimed to explore the effect of CBSM on neurologic recovery and psychosomatic health in AIS patients. Totally, 176 naive AIS patients were randomized into routine care (RC) group (n=88) and CBSM group (n=88) to receive a 3-month corresponding intervention. Modified Rankin scale (mRS) scores at the first month after discharge (M1) (P=0.008) and the third month after discharge (M3) (P=0.016) were lower in the CBSM group than in the RC group. The proportion of AIS patients with mRS score >2 at M3 was reduced in CBSM group vs RC group (P=0.045). Hospital anxiety depression scale (HADS)-anxiety score at M3 (P=0.016), HADS-depression score at M3 (P=0.005), and depression rate at M3 (P=0.021) were decreased in the CBSM group vs the RC group. EuroQol-5 dimension scores at M1 (P=0.024) and M3 (P=0.012) were decreased, while EuroQol-visual analogue scale score at M3 (P=0.026) was increased in the CBSM group vs the RC group. By subgroup analyses, CBSM had favorable outcomes in AIS patients with age ≤65 years. CBSM was beneficial to neurologic recovery and distress relief in AIS patients with an education level of middle school or above, and to health status in those with an education level of primary school or uneducated. In conclusion, CBSM benefitted neurologic recovery and psychosomatic health in AIS patients with minor neurological deficits, however, further studies should verify these results with a larger sample size and longer follow-up.
Diagnostic value of serum inflammatory markers in predicting early refractoriness of transarterial chemoembolization in patients with Barcelona Clinic Liver Cancer Stage 0, A, and B hepatocellular carcinoma.
Yang J, Zhang Y, Kong Y … +6 more , Lin J, Zhu G, Zhang H, Yu Z, Liu P, Xia J
Braz J Med Biol Res · 2024 · PMID 39258671 · Full text
Transarterial chemoembolization (TACE) is an established therapeutic strategy for intermediate stage Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC). However, patients who are early refractory to TACE...
Transarterial chemoembolization (TACE) is an established therapeutic strategy for intermediate stage Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC). However, patients who are early refractory to TACE may not benefit from repeated TACE treatment. Our primary objective was to assess the diagnostic value of inflammatory markers in identifying early TACE refractory for patients with early (BCLC 0 and A) or intermediate (BCLC B) stage HCC. We retrospectively reviewed the HCC patients who underwent TACE as the initial treatment in two hospitals. Patients with early TACE refractoriness had significantly poorer median overall survival (OS) (16 vs 40 months, P<0.001) and progression-free survival (PFS) (7 vs 23 months, P<0.001) compared to TACE non-refractory patients. In the multivariate regression analysis, tumor size (P<0.001), bilobular invasion (P=0.007), high aspartate aminotransferase-to-platelet ratio index (APRI) (P=0.007), and high alpha fetoprotein (AFP) level (P=0.035) were independent risk factors for early TACE refractoriness. The predictive model showcasing these factors exhibited high ability proficiency, with an area under curve (AUC) of 0.833 (95%CI=0.774-0.892) in the training cohort, 0.750 (95%CI: 0.640-0.861) in the internal-validation cohort, and 0.733 (95%CI: 0.594-0.872) in the external-validation cohort. Calibration curve analysis revealed good agreement between the actual and predicted probabilities of early TACE refractoriness. Our preliminary study estimated the potential value of inflammatory markers in predicting early TACE refractoriness and provides a predictive model to assist in identifying patients who may not benefit from repeat TACE treatment.
Decoding potential targets and pharmacologic mechanisms of curcumin in treating non-small cell lung carcinoma via bioinformatics and molecular docking.
Li J, Zhang Z, Zhao J … +9 more , Liu S, Feng C, Deng H, Liu D, Zeng J, Yu Q, Zhou D, Zhu M, Liu Y
Braz J Med Biol Res · 2024 · PMID 39258670 · Full text
Emerging evidence demonstrates that curcumin has an inhibitory effect on non-small cell lung cancer (NSCLC), and its targets and mechanism of action need further exploration. The goal of this study was to explore the pot...
Emerging evidence demonstrates that curcumin has an inhibitory effect on non-small cell lung cancer (NSCLC), and its targets and mechanism of action need further exploration. The goal of this study was to explore the potential targets and mechanism of curcumin against NSCLC by network pharmacology, bioinformatics, and experimental validation, thereby providing more insight into combination treatment with curcumin for NSCLC in preclinical and clinical research. Curcumin targets against NSCLC were predicted based on HIT2.0, STD, CTD, and DisGeNET, and the core targets were analyzed via protein-protein interaction network construction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking. The gene expression levels of samples in A549 cells, NCI-H460, and curcumin treated groups were detected by real-time quantitative PCR. A total of 67 common targets between curcumin and NSCLC were collected by screening public databases. GO and KEGG analysis suggested that curcumin treatment of NSCLC mainly involves cancer-related pathways, such as PI3K-AKT signaling pathway, Foxo signaling pathway, microRNAs, MAPK signaling pathway, HIF-1 signaling pathway, etc. The targets with the highest degree were identified through the PPI network, namely CASP3, CTNNB1, JUN, IL6, MAPK3, HIF1A, STAT3, AKT1, TP53, CCND1, VEGFA, and EGFR. The results of the in vitro experiments showed that curcumin treatment of NSCLC down-regulated the gene expressions of CCND1, CASP3, HIF1A, IL-6, MAPK3, STAT3, AKT1, and TP53. Our findings revealed that curcumin functions as a potential therapeutic candidate for NSCLC by suppressing multiple signaling pathways and interacting with multiple gene targets.
Resveratrol as a cardioprotective adjuvant for 5-fluorouracil in the treatment of gastric cancer cells.
Liu L, Wang Y, Dong Y … +3 more , Lin S, Guan W, Song J
Braz J Med Biol Res · 2024 · PMID 39258669 · Full text
The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known...
The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.
Inhibition of the ITGB1 gene attenuates crystalline silica-induced pulmonary fibrosis via epithelial-mesenchymal transformation.
Li H, Xu S, Li X … +6 more , Wang P, Hu M, Li N, Zhou Q, Chang M, Yao S
Braz J Med Biol Res · 2024 · PMID 39258668 · Full text
Silicosis is a systemic disease caused by long-term exposure to high concentrations of free silica dust particles in the workplace. It is characterized by a persistent inflammatory response, fibroblast proliferation, and...
Silicosis is a systemic disease caused by long-term exposure to high concentrations of free silica dust particles in the workplace. It is characterized by a persistent inflammatory response, fibroblast proliferation, and excessive collagen deposition, leading to pulmonary interstitial fibrosis. Epithelial interstitial transformation (EMT) can cause epithelial cells to lose their tight junctions, cell polarity, and epithelial properties, thereby enhancing the properties of interstitial cells, which can lead to the progression of fibrosis and the formation of scar tissue. Integrin 1 (ITGB1) is considered an important factor for promoting EMT and tumor invasion in a variety of tumors and also plays an important role in the progression of fibrotic diseases. Therefore, ITGB1 can be used as a potential target for the treatment of silicosis. In this study, we found that silica exposure induced epithelial-mesenchymal transformation in rats and that the expression of integrin ITGB1 was elevated along with the EMT. We used CRISPR/Cas9 technology to construct integrin ITGB1 knockdown cell lines for in vitro experiments. We compared the expression of the EMT key proteins E-cadherin and vimentin in the ITGB1 knockdown cells and wild-type cells simultaneously stimulated by silica and detected the aggregation point distribution of E-cadherin and vimentin in the cells using laser confocal microscopy. Our results showed that ITGB1 knockout inhibited the ITGB1/ILK/Snail signaling pathway and attenuated the EMT occurrence compared to control cells. These results suggested that ITGB1 is associated with silica-induced EMT and may be a potential target for the treatment of silicosis.
The role and mechanisms of cordycepin in inhibiting cancer cells.
Yu G, Peng J, Li L … +3 more , Yu W, He B, Xie B
Braz J Med Biol Res · 2024 · PMID 39194034 · Full text
With the escalating incidence and mortality rates of cancer, there is an ever-growing emphasis on the research of anticancer drugs. Cordycepin, the primary nucleoside antibiotic isolated from Cordyceps militaris, has eme...
With the escalating incidence and mortality rates of cancer, there is an ever-growing emphasis on the research of anticancer drugs. Cordycepin, the primary nucleoside antibiotic isolated from Cordyceps militaris, has emerged as a remarkable agent for cancer prevention and treatment. Functioning as a natural targeted antitumor drug, cordycepin assumes an increasingly pivotal role in cancer therapy. This review elucidates the mechanisms of cordycepin in inhibiting tumor cell proliferation, inducing apoptosis, as well as its capabilities in suppressing angiogenesis and metastasis. Moreover, the immunomodulatory effects of cordycepin in cancer treatment are explored. Additionally, the current status, challenges, and future prospects of cordycepin application in clinical trials are briefly discussed. The objective is to provide a valuable reference for the utilization of cordycepin in cancer treatment.
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