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Introduction: Pulmonary fibrosis (PF) and tissue remodeling can greatly impair pulmonary function and often lead to fatal outcomes. Methodology: In the present study, we explored a novel molecular interplay of long noncoding (Lnc) RNA CBR3-AS1/ miRNA-29/ FIZZ1 axis in moderating the inflammatory processes, immunological responses, and oxidative stress pathways in bleomycin (BLM)-induced lung fibrosis. Furthermore, we investigated the pharmacological potential of Trimetazidine (TMZ) in ameliorating lung fibrosis. Results: Our results revealed that the BLM-treated group exhibited a significant upregulation in the expression of epigenetic regulators, lncRNA CBR3-AS1 and FIZZ1, compared to the control group (P<0.0001), along with the downregulation of miRNA-29 expression. Furthermore, Correlation analysis showed a significant positive association between lnc CBR3-AS1 and FIZZ1 (R=0.7723, p<0.05) and a significant negative association between miRNA-29 and FIZZ1 (R=-0.7535, p<0.05), suggesting lnc CBR3-AS1 as an epigenetic regulator of FIZZ1 in lung fibrosis. BLM treatment significantly increased the expression of Notch, Jagged1, Smad3, TGFB1, and hydroxyproline. Interestingly, the administration of TMZ demonstrated the ability to attenuate the deterioration effects caused by BLM treatment, as indicated by biochemical and histological analyses. Our investigations revealed that the therapeutic potential of TMZ as an antifibrotic drug could be ascribed to its ability to directly target the epigenetic regulators lncRNA CBR3-AS1/ miRNA-29/ FIZZ1, which in turn resulted in the mitigation of lung fibrosis. Histological and immunohistochemical analyses further validated the potential antifibrotic effects of TMZ by mitigating the structural damage associated with fibrosis. Discussion: Taken together, our study showed for the first time the interplay between epigenetic lncRNAs CBR3-AS1 and miRNA-29 in lung fibrosis and demonstrated that FIZZ1 could be a downregulatory gene for lncRNA CBR3-AS1 and miRNA-29. Our key findings demonstrate that TMZ significantly reduces the expression of fibrotic, oxidative stress, immunomodulatory, and inflammatory markers, along with epigenetic regulators associated with lung fibrosis. This validates its potential as an effective antifibrotic agent by targeting the CBR3-AS1/miRNA-29/FIZZ1 axis.

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Patients with rare genetic muscle-wasting disorders (MWDs) often experience significant motor function impairments, making effective management strategies crucial for improving their quality of life. This systematic review and meta-analysis aimed to evaluate the impact of physiotherapeutic interventions on motor outcomes in this patient population.  A comprehensive literature search was conducted to identify randomized controlled trials (RCTs) and cohort-based studies that assessed physiotherapeutic interventions in patients with rare genetic MWDs. The primary outcome measure was the 6-minute walk test (6MWT). A random effects model was employed to calculate the mean difference (MD) and 95% confidence interval (CI).  Nine studies were selected for inclusion, and most demonstrated observable improvement in different facets of individuals with MWDs using physiotherapy. The meta-analysis of RCTs showed that physiotherapy statistically improved 6MWT performance (MD: -35.25 meters; 95% CI: -54.14 to -16.37) with low heterogeneity (Tau² = 0.00; Chi² = 0.48, df = 2, P = 0.79; I² = 0%). Similarly, the cohort-based studies demonstrated an overall MD (MD: -10.00; 95% CI: -11.07 to -8.93), with low heterogeneity (Tau² = 0.00; Chi² = 0.01, df = 1, P = 0.94; I² = 0%). Both analyses indicated significant improvements in 6MWT performance (RCTs: Z = 3.66, P = 0.0003; cohort-based: Z = 18.26, P < 0.00001). Physiotherapeutic interventions significantly enhanced motor function in patients with rare genetic MWDs, as evidenced by improved 6MWT performance. Exercise and intensive physiotherapy programs were particularly effective, although the benefits varied depending on the specific intervention and patient population. These findings support incorporating tailored physiotherapeutic strategies in MWD management to improve motor outcomes and overall quality of life.

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Microtubules are highly dynamic structures and constitute a crucial component of the cellular cytoskeleton. Besides, topoisomerases (Topo) play a fundamental role in maintaining the appropriate structure and organization of DNA. On the other hand, dual mechanism drug candidates for cancer treatment primarily aim to enhance the efficacy of cancer treatment and potentially overcome drug resistance. Hence, this work was tailored to design and synthesize new multi-target tetrabromophthalimide derivatives (2a-2k) that are capable of inhibiting the colchicine binding site (CBS) and topoisomerase II (Topo-II). The conducted in vitro studies showed that compound 2f showed the lowest IC50 value (6.7 µg mL-1) against the MDA-MB-468 cancer cell line. Additionally, compound 2f prompted upregulation of pro-apoptotic markers (caspases 3, 7, 8, and 9, Bax and p53). Moreover, some anti-apoptotic proteins (MMP2, MMP9, and BCL-2) were downregulated by compound 2f treatment. Besides, the colchicine binding assay showed that compounds 2f and 2k displayed promising inhibitory potential with IC50 values of 1.92 and 4.84 µg mL-1, respectively, in comparison with colchicine (1.55 µg mL-1). Furthermore, the Topo-II inhibition assay displayed the prominent inhibitory potential of compound 2f with an IC50 value of 15.75 µg mL-1, surpassing the IC50 of etoposide (20.82 µg mL-1). Cell cycle analysis revealed that compound 2f induced cell cycle arrest at both the G0-G1 and G2-M phases. The new candidates were docked against both the CBS (PDB ID: 5XIW) and Topo-II (PDB ID: 5CDP) targets to investigate their binding interactions and affinities as well. Accordingly, the synthesized compounds could serve as promising multi-target anticancer candidates with eligible apoptotic activity.

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Introduction: Second-Generation Antipsychotics (SGAs) are widely used for treating psychiatric disorders due to their favorable side effect profile compared to First-Generation Antipsychotics (FGAs). However, SGAs are associated with significant metabolic side effects. This study aims to explore the sociodemographic and health differences between individuals using SGAs and those not using them. Methods: A comparative cross-sectional study was conducted with 148 participants, including 102 SGA users and 46 non-users. Data were collected from patients and medical records, encompassing sociodemographic factors and health variables including diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia, waist circumference, fasting blood glucose, cholesterol, triglycerides, HDL, LDL, and BMI. Statistical analyses included chi-square and Fisher's exact tests to compare the two groups. Results: SGA users had higher rates of overweight and obesity compared to non-users (p = 0.000), with 30.4% overweight and 29.4% obese among SGA users versus 21.7% overweight and 4.3% obese among non-users. A higher prevalence of cardiovascular disease was observed in SGA users (11.8% vs. 2.2%, p = 0.076). Although not statistically significant, trends indicated higher rates of diabetes mellitus and hyperlipidemia in non-users (30.4% vs. 18.6%, p = 0.110 and 7% vs. 0%, p = 0.083, respectively). Conclusion: This study highlights significant differences in BMI and cardiovascular disease prevalence between SGA users and non-users, reinforcing the need for comprehensive metabolic monitoring in patients treated with SGAs. The findings underscore the importance of considering sociodemographic factors in managing the health risks associated with SGA use. Further research with larger sample sizes and longitudinal designs is warranted to better understand these associations and develop targeted interventions.

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Dengue virus (DENV) infection is a worldwide public health concern infecting approximately 400 million individuals and about 40,000 mortalities yearly. Despite this, no licensed or readily available antiviral medication is currently available specifically for DENV infection, and therapy is typically symptomatic. Therefore, the objective of the study was to investigate the antiviral activity of Beta vulgaris L. phytoconstituents against DENV-2 targeting NS3 protein. The antiviral activity of phytochemicals was examined through virtual ligand-based screening, antiviral inhibition and dosage response assays, western blotting analysis and MD simulations. We conducted toxicological, and pharmacokinetic analysis to assess plant-based natural compound's efficacy, safety, and non-toxic doses. Molecular docking and MD simulation results revealed that the nonstructural protein-3 (NS3) might prove as a funamental target for Betanin and Glycine Betaine against Dengue virus. Betanin and Glycine betaine were initially studied for their non-toxic doses in HeLa, CHO, and Vero cells via MTT assay. HeLa cells were transiently transfected with cloned vector pcDNA3.1/Zeo(+)/DENV-2 NS3 along with non-toxic doses (80 µM-10 µM) of selected phytochemicals. The dose-response assay illustrated downregulated expression of DENV-2 NS3 gene after administration of Betanin (IC50 = 4.35 µM) and Glycine Betaine (IC50 = 4.49 µM). Dose response analysis of Betanin (80 µM-10 µM) depicted the significant inhibition of NS3 protein expression as well. These results suggested downregulated expression of DENV-2 NS3 at mRNA and protein level portraying the DENV replication inhibition. Based on our study findings, NS3 protease is depicted as distinctive DENV-2 inhibitor target. We will channel our study further into in vitro characterization employing the mechanistic study to understand the role of host factors in anti-flavi therapeutic.

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Long non-coding RNAs (lncRNAs) significantly influence gene regulation across epigenetic, transcriptional, and post-transcriptional levels through their interactions with DNA, RNA, and proteins. There is growing evidence of lncRNAs' critical roles in the emergence and progression of various diseases, including urological tumors (UTs), such as cancers of the kidney, bladder, and prostate. Research increasingly links lncRNA dysregulation to diverse cellular processes like invasion, metastasis, apoptosis, and chromatin remodeling. Among these, HOTAIR stands out for its pivotal role in oncogenesis, impacting treatment resistance, cell migration, proliferation, survival, and genomic integrity. This review provides an overview of HOTAIR's functions, its identification, and its biological significance. Furthermore, it delves into HOTAIR's involvement in UTs, underlining its potential as a therapeutic target and biomarker for innovative approaches to treating these cancers.

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Intestinal inflammation is one of the main health challenges affecting the quality of life of millions of people worldwide. Accumulating evidence introduces several flavonoids with multifaceted therapeutic properties in inflammatory diseases including intestinal inflammation. Herein, we examined potential anti-inflammatory properties of 5,4'-dihydroxy-6,8-dimethoxy7-O-rhamnosylflavone (DDR) flavone derived from Indigofera aspalathoides Vahl (I. aspalathoides Vahl) on lipopolysaccharide (LPS)-induced intestinal inflammation and injury in mice. Oral DDR treatment decreased serum levels of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1ß. It reduced oxidative stress through augmenting the activities of catalase (CAT) and superoxide dismutase (SOD) and reducing the level of malondialdehyde (MDA) in the duodenum and colon tissues. Moreover, DDR enhanced the activities of digestive enzymes including trypsin, pancreatic lipase, and amylase, and increased the production of short-chain fatty acids (SCFAs) by colon microbiota. Histopathological investigation of duodenum and colon revealed that DDR inhibited inflammatory infiltration and largely restored mucosal architecture and protected lining integrity. Importantly, DDR suppressed activation of nuclear factor-κB (NF-κB) signaling pathway through reduced expression of Toll-like receptor 4 (TLR4) and expression and phosphorylation of P65. The current study identified DDR as anti-inflammatory flavonoid capable of ameliorating LPS-induced intestinal inflammation through suppression of NF-κB signaling.

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Background: Gestational diabetes mellitus (GDM) is a condition that can have negative impacts on both mother and baby. Detecting GDM early is crucial, and fasting plasma glucose (FPG) has been suggested as a possible screening method. This retrospective cross-sectional study aims to investigate potential risk factors and complications associated with GDM. Additionally, it aims to establish the diagnostic performance of predictive factors as a screening method for GDM. Methods: Data were collected from the medical records of 247 pregnant women who visited outpatient Obstetrics clinics between 2021 and 2022. The study investigated potential risk factors and complications associated with GDM, including impaired fasting glucose/impaired glucose tolerance (IFG/IGT), family history of diabetes mellitus (DM), and medical conditions. Moreover, the study evaluated the diagnostic performance of potential predictors as screening techniques for GDM. Results: The study found that IFG/IGT (P<0.001), a history of GDM (P<0.001), and a family history of DM (P=0.022) were significant factors associated with GDM. Healthy individuals had a lower risk of developing GDM (P<0.001). No significant correlation was found between GDM and macrosomia, hypertension, polycystic ovarian syndrome, or other obstetric complications. Although a weak association was observed between fasting blood glucose levels during the first trimester and GDM, it was not significant. Conclusion: In conclusion, this study found that IFG/IGT and a past history of GDM were significantly associated with GDM. Additionally, a family history of diabetes increased the likelihood of developing GDM, while no significant association was found between GDM and other obstetric complications. Although a weak association was observed between fasting blood glucose levels during the first trimester and GDM, it was not statistically significant.

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Background: Semaglutide is a glucagon-like peptide-1 receptor agonists (GLP-1-RAs) approved for the treatment of type 2 diabetes mellitus (T2DM) at doses up to 1 mg. The results from randomized control trials and real-world studies revealed that weekly semaglutide was associated with significant improvements in HbA1c and body weight. To our knowledge, no study assessed the effectiveness of using semaglutide for patients with T2DM in the Saudi population. We aim to assess the effectiveness of once weekly SC 0.5 and 1 mg of semaglutide on HbA1c and weight reduction in patients with T2DM in the Saudi population within 12 months of use, evaluate the predictors of response, and compare the effect of the two doses. Method: This is a retrospective cohort study conducted at Security Force Hospital in Riyadh, Saudi Arabia. Using electronic medical records of patients with type two diabetes who received semaglutide 0.5 or 1 mg for a total duration of at least 12 months of use. Results: Within the study period of semaglutide use, HbA1c significantly decreased from baseline by -2.1% (-2.3 to -1.91, 95% CI) (P <0.001). While the mean change in weight was -6.19 kg (-6.66 to -5.72, 95% CI) (P<0.001). Moreover, BMI, FBG, total cholesterol, LDL, and TG all decreased significantly from baseline (p<0.001). When comparing the sub-groups of 0.5 and 1 mg doses, although results were numerically favorable of 1 mg, there were no statistically significant differences in HbA1c % (-2.1 ± 1.8 vs. -2.1 ± 1.9, p-value= 0.934, respectively), and weight (-6.1 ± 5 vs. -6.2 ± 4.4 kg, p-value=0.837, respectively). Significant predictors of HbA1c reduction were the duration of DM, baseline HbA1c, and insulin therapy. While the significant predictor for weight reduction was insulin therapy. Conclusion: This study is document the effectiveness of once-weekly SC semaglutide on glycemic control and weight loss in real-world practice. We recommend a starting goal dose of 0.5 mg and gradual increase of dose based individual patient response. further studies are needed to assess the effectiveness and tolerability of various semagltude doses.

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Background: Brucellosis is a bacterial zoonotic infection that is endemic in Saudi Arabia and associated with clinical and economic impacts. Several studies from countries endemic for brucellosis evaluated the knowledge and attitude of livestock farmers regarding brucellosis. However, no such study was conducted in Saudi Arabia. This study aimed to evaluate the knowledge, attitude, and practice of livestock farmers and meat handlers in Saudi Arabia. Methods: This was a cross-sectional questionnaire-based study, where participants were interviewed in-person in Arabic in livestock markets between September-December 2023. Convenient sampling was utilized. The questionnaire included basic demographics and questions to assess the knowledge, attitude, and practice toward personal protection and protection of the animals from brucellosis. The questionnaire was adapted from a previously validated survey and included 59 questions. Providing at least one correct answer to a certain question indicated a good knowledge about this item or a safe practice. The participants were divided into: farmers (shepherds working for the animal owners), commercial animal owners (those who rent a stockyard in the livestock market and employ farmers to sell their animals), and private animal owners (owners of private farms from which they sell their animals). Results: 545 participants were interviewed (n = 291 farmers, n = 118 commercial animal owners, n = 113 private animal owners, and n = 23 animal slaughterhouse workers). >90% have heard of brucellosis. Lack of education and short experience (<5 years) of working with livestock were negatively associated with good knowledge of brucellosis symptoms and transmission (OR, 0.30; 95%CI, 0.10-0.94; p = 0.038 and OR, 0.23; 95%CI, 0.08-0.62; p = 0.004, respectively). Taking sick animals to the veterinarian was reported by 61.2%, whereas 36.4% follow safe practices when disposing of aborted fetuses. While 34% consume raw milk, only 10% consume rare/medium-rare meat. 51.2% acknowledged the need for more information on brucellosis. Conclusion: This study revealed the need to augment the knowledge of people working with animals, particularly those with no school education and those with short work experience, via providing educational visits or materials or through veterinarians. This should help them identify human and animal brucellosis symptoms and increase the knowledge on how to protect oneself and animals from this disease.

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A series of benzoquinoline-employing heterocycles was synthesized by treating 3-chlorobenzo[f]quinoline-2-carbaldehyde with N-phenyl-3-methylpyrazolone, 4-aminoacetophenone, 1,2-diaminoethane, and 2-cyanoethanohydrazide. Also, pyridine, chromene, α,ß-unsaturated nitrile, thiosemicarbazone, and 1,2-bis-aryl hydrazine derivatives were prepared from the cyanoethanohydrazone obtained. The DFT calculations and experiment outcomes were consistent. In vitro screening of their antiproliferative efficacy was examined against HCT116 and MCF7 cancer cell lines. The pyrazolone 2 and cyanoethanohydrazone 5 derivatives exhibited the most potency, which was demonstrated by their molecular docking towards the CDK-5 enzyme. The binding energies of compounds 2 and 5 were - 6.6320 kcal/mol (with RMSD of 0.9477 Å) and - 6.5696 kcal/mol (with RMSD of 1.4889 Å), respectively, which were near to that of co-crystallized ligand (EFP). This implies a notably strong binding affinity towards the CDK-5 enzyme. Thus, pyrazolone derivative 2 would be considered a promising candidate for further optimization to develop new chemotherapeutic agents. In addition, the ADME (absorption, distribution, metabolism, and excretion) analyses displayed its desirable drug-likeness and oral bioavailability properties.

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Background: It has been suggested that metabolic syndrome (MetS) accelerates the aging process, potentially contributing to the development of age-related complications. Available studies examining the relation of MetS to telomere length (TL), a putative biological marker of aging, have yielded inconclusive findings. This meta-analysis was performed to investigate the association between MetS and TL. Methods: A comprehensive systematic search was conducted in PubMed and Scopus databases to identify relevant literature published up to February 2024. Standard mean difference (SMD) and standardized beta coefficient (ß) with their 95% confidence intervals (CI) were used as effect sizes to measure the associations using the random effects model. Results: A total of nine studies, comprising a total sample size of 8,606 participants, were eligible for the meta-analysis. No significant difference in mean TL was found between patients with and without MetS (SMD = -0.03, 95%CI = -0.17 to 0.10), with a significant heterogeneity across the studies (I 2 = 89.7.0%, p ≤ 0.001). In contrast, it was revealed that MetS is negatively related to TL (ß = -0.08, 95%CI = -0.15 to -0.004). In the subgroup analysis, this finding was supported by the International Diabetes Federation (IDF) definition of MetS. Conclusion: This meta-analysis highlighted that MetS may be linked to a shorter TL. Additional studies are required to confirm this finding.

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Conversion of toxic nitroarenes into less toxic aryl amines, which are the most suitable precursors for different types of compounds, is done with various materials which are costly or take more time for this conversion. In this regards, a silica@poly(chitosan-N-isopropylacrylamide-methacrylic acid) Si@P(CS-NIPAM-MAA) Si@P(CNM) core-shell microgel system was synthesized through free radical precipitation polymerization (FRPP) and then fabricated with palladium nanoparticles (Pd NPs) by in situ-reduction method to form Si@Pd-P(CNM) and characterized with XRD, TEM, FTIR, SEM, and EDX. The catalytic efficiency of Si@Pd-P(CNM) hybrid microgels was studied for reduction of 4-nitroaniline (4NiA) under diverse conditions. Different nitroarenes were successfully transformed into their corresponding aryl amines with high yields using the Si@Pd-P(CNM) system as catalyst and NaBH4 as reductant. The Si@Pd-P(CNM) catalyst exhibited remarkable catalytic efficiency and recyclability as well as maintaining its catalytic effectiveness over multiple cycles.

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Wound healing is a critical process in tissue repair following injury, and traditional herbal therapies have long been utilized to facilitate this process. This review delves into the mechanistic understanding of the significant contribution of pharmacologically demonstrated natural products in wound healing. Natural products, often perceived as complex yet safely consumed compared to synthetic chemicals, play a crucial role in enhancing the wound-healing process. Drawing upon a comprehensive search strategy utilizing databases such as PubMed, Scopus, Web of Science, and Google Scholar, this review synthesizes evidence on the role of natural products in wound healing. While the exact pharmacological mechanisms of secondary metabolites in wound healing remain to be fully elucidated, compounds from alkaloids, phenols, terpenes, and other sources are explored here to delineate their specific roles in wound repair. Each phytochemical group exerts distinct actions in tissue repair, with some displaying multifaceted roles in various pathways, potentially enhancing their therapeutic value, supported by reported safety profiles. Additionally, these compounds exhibit promise in the prevention of keloids and scars. Their potential alongside economic feasibility may propel them towards pharmaceutical product development. Several isolated compounds, from natural sources, are undergoing investigation in clinical trials, with many reaching advanced stages.

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According to findings, long non-coding RNAs (lncRNAs) serves an integral part in growth and development of a variety of human malignancies, including Hepatoblastoma (HB). HB is a rare kind of carcinoma of the liver that mostly affects kids and babies under the age of three. Its manifestations include digestive swelling, abdominal discomfort, and losing weight. This thorough investigation digs into the many roles that lncRNAs serve in HB, giving views into their varied activities as well as possible therapeutic consequences. The function of lncRNAs in HB cell proliferation, apoptosis, migratory and penetrating capacities, epithelial-mesenchymal transition, and therapy tolerance is discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell processes such as angiogenesis, apoptosis, immunity, and growth. Circulating lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. In addition to their diagnostic utility, lncRNAs provide curative opportunities as locations and actors, contributing to the expanding landscape of cancer research. Several HB-linked lncRNAs have been demonstrated to exhibit abnormal expression and are involved in tumor-like characteristics via DNA, RNA, or protein binding or encoding short peptides. As a result, a better knowledge of lncRNA instability might bring fresh perspectives into HB etiology as well as innovative strategies for HB early diagnosis and therapy. We describe the abnormalities of lncRNA expression in HB and their tumor-suppressive or carcinogenic activities during HB carcinogenesis in this study. Furthermore, we explore lncRNAs' diagnostic and therapeutic possibilities in HB.

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BACKGROUND: Despite the progress in comprehending molecular design principles and biochemical processes associated with thrombin inhibition, there is a crucial need to optimize efforts and curtail the recurrence of synthesis-testing cycles. Nitrogen and N-heterocycles are key features of many anti-thrombin drugs. Hence, a pragmatic analysis of nitrogen and N-heterocycles in thrombin inhibitors is important throughout the drug discovery pipeline. In the present work, the authors present an analysis with a specific focus on understanding the occurrence and distribution of nitrogen and selected N-heterocycles in the realm of thrombin inhibitors. RESEARCH DESIGN AND METHODS: A dataset comprising 4359 thrombin inhibitors is used to scrutinize various categories of nitrogen atoms such as ring, non-ring, aromatic, and non-aromatic. In addition, selected aromatic and aliphatic N-heterocycles have been analyzed. RESULTS: The analysis indicates that ~62% of thrombin inhibitors possess five or fewer nitrogen atoms. Substituted N-heterocycles have a high occurrence, like pyrrolidine (23.24%), pyridine (20.56%), piperidine (16.10%), thiazole (9.61%), imidazole (7.36%), etc. in thrombin inhibitors. CONCLUSIONS: The majority of active thrombin inhibitors contain nitrogen atoms close to 5 and a combination of N-heterocycles like pyrrolidine, pyridine, piperidine, etc. This analysis provides crucial insights to optimize the transformation of lead compounds into potential anti-thrombin inhibitors.

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Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund's complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.

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Currently, it has been stated that psychiatric and psychological problems are equally paramount aspects of the clinical modulation and manifestation of both the central nervous and digestive systems, which could be used to restore balance. The present narrative review aims to provide an elaborate description of the bio-psycho-social facets of refractory functional gastrointestinal disorders, psychiatrists' role, specific psychiatric approach, and the latest psychiatric and psychological perspectives on practical therapeutic management. In this respect, "psyche," "psychiatry," "psychology," "psychiatrist," "psychotropic," and "refractory functional gastrointestinal disorders" (as the keywords) were searched in relevant English publications from January 1, 1950, to March 1, 2024, in the PubMed, Web of Science, Scopus, EMBASE, Cochrane Library, and Google Scholar databases. Eventually, the narrative technique was adopted to reach a compelling story with a high level of cohesion through material synthesis. The current literature recognizes the brain-gut axis modulation as a therapeutic target for refractory functional gastrointestinal disorders and the bio-psycho-social model as an integrated framework to explain disease pathogenesis. The results also reveal some evidence to affirm the benefits of psychotropic medications and psychological therapies in refractory functional gastrointestinal disorders, even when psychiatric symptoms were absent. It seems that psychiatrists are required to pay higher levels of attention to both the assessment and treatment of patients with refractory functional gastrointestinal disorders, accompanied by educating and training practitioners who take care of these patients.

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Objective: This study investigated the impact of wearable technologies, particularly advanced biomechanical analytics and machine learning, on sports performance monitoring and intervention strategies within the realm of physiotherapy. The primary aims were to evaluate key performance metrics, individual athlete variations and the efficacy of machine learning-driven adaptive interventions. Methods: The research employed an observational cross-sectional design, focusing on the collection and analysis of real-world biomechanical data from athletes engaged in sports physiotherapy. A representative sample of athletes from Bahawalpur participated, utilizing Dring Stadium as the primary data collection venue. Wearable devices, including inertial sensors (MPU6050, MPU9250), electromyography (EMG) sensors (MyoWare Muscle Sensor), pressure sensors (FlexiForce sensor) and haptic feedback sensors, were strategically chosen for their ability to capture diverse biomechanical parameters. Results: Key performance metrics, such as heart rate (mean: 76.5 bpm, SD: 3.2, min: 72, max: 80), joint angles (mean: 112.3 degrees, SD: 6.8, min: 105, max: 120), muscle activation (mean: 43.2%, SD: 4.5, min: 38, max: 48) and stress and strain features (mean: [112.3 ], SD: [6.5 ]), were analyzed and presented in summary tables. Individual athlete analyses highlighted variations in performance metrics, emphasizing the need for personalized monitoring and intervention strategies. The impact of wearable technologies on athletic performance was quantified through a comparison of metrics recorded with and without sensors. Results consistently demonstrated improvements in monitored parameters, affirming the significance of wearable technologies. Conclusions: The study suggests that wearable technologies, when combined with advanced biomechanical analytics and machine learning, can enhance athletic performance in sports physiotherapy. Real-time monitoring allows for precise intervention adjustments, demonstrating the potential of machine learning-driven adaptive interventions.

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Chicory (Cichorium endivia L. divaricatum) is a renowned medicinal plant traditionally used for various ailments, yet the pharmacological potential of its roots, particularly in terms of antitumor activity, remains elusive. In the present study, we explore, for the first time, the metabolomic profile of ethanolic extract from Cichorium endivia roots (CIR) and further unveil its antiproliferative potential. The untargeted phytochemical analysis UPLC/T-TOF-MS/MS identified 131 metabolites in the CIR extract, covering acids, amino acids, flavonoids, alkaloids, nucleotides, and carbohydrates. The antiproliferative activity of the CIR extract was tested in 14 cancer cell lines, revealing significant cytotoxicity (IC50: 2.85-29.15 µg mL-1) and a high selectivity index. Among the cells examined, the CIR extract recorded the most potent antiproliferative activity and selectivity toward HepG2 and Panc-1 cells, with an IC50 of 2.85 µg mL-1 and 3.86 µg mL-1, respectively, and SI > 10. Insights into the mode of action of the antiproliferative activity revealed that CIR extract induces cell arrest in the S phase while diminishing cell distribution in the G0/G1 and G2/M phases in HepG-2 and Panc-1 cells. Flow cytometric and RT-PCR analysis revealed that the CIR extract significantly triggers apoptosis and modulates the expression of pro-apoptotic and anti-apoptotic genes. Furthermore, the CIR extract exhibited a pronounced anti-inflammatory activity, as evidenced by down-regulating key cytokines in LPS-induced RAW 264.7 cells and selectively inhibiting the COX-2 enzyme. Finally, the CIR extract showed a robust total antioxidant capacity, together with potent free radicals and metal scavenging properties, highlighting its role in alleviating oxidative stress. Taken together, this study highlights the multifaceted therapeutic potential of CIR extract as a natural-based antitumor supplement.