Navel orange peel ethanolic extract and naringin ameliorate CFA-induced arthritis in Wistar rats through their modulatory effects on Th1/Th2/Th17 cytokines and oxidative stress.

Rheumatoid arthritis (RA) is an autoimmune illness affecting joint articulations, leading to a disability state. Currently, there is no satisfying optimal therapy except for immunosuppressants, which have variable and bad effects after long-term use. Hence, researchers have attempted to develop other alternative, safer, and more effective natural treatment agents that are effective and without undesirable effects. The objective of this research is to assess the antiarthritic properties of navel orange peel ethanolic extract (NOPEE) and naringin (NAR) in experimentally induced RA in male Wistar rats. RA was induced via two successive subcutaneous injections of 0.1 mL complete Freund's adjuvant (CFA) into a footpad of the right hind leg. The arthritic rats were orally treated with 100 mg/kg body weight (b.w.)/day of NOPEE or with 25 mg/kg b.w./day of NAR for 14 days. Results showed that treatment with NOPEE or NAR obviously counteracted the increased ankle joint circumference, inflammatory cell infiltration, pannus development, cartilage degradation, and synovial hyperplasia that developed in CFA-induced arthritic rats. Additionally, the elevation of serum rheumatoid factor (RF), prostaglandin E2 (PGE-2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-17 (IL-17) were significantly declined in parallel to enhanced level of serum interleukin-4 (IL-4). Furthermore, NOPEE and NAR supplementation, reversed the negative oxidative effects of lipid peroxidation (LPO), nitric oxide (NO), as well as improved the antioxidant glutathione level (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) activities. Overall, the anti-arthritic effects of NOPEE and NAR may be mediated through their modulatory effects on T helper (Th)1/Th2/Th17 cytokines, oxidative stress, and the antioxidant defense system.

Improvement of Vicia faba plant tolerance under salinity stress by the application of thiamine and pyridoxine vitamins.

Enhancement of plant growth at early growth stages is usually associated with the stimulation of various metabolic activities, which is reflected on morphological features and yield quantity and quality. Vitamins is considered as anatural plant metabolites which makes it a safe and ecofriendly treatment when used in appropriate doses, for that this research aimed to study the effect of two different vitamin B forms (thiamine and pyridoxine) on Vicia faba plants as agrowth stimutator in addition to study it's effect on plant as astrong antioxidant under salinity stress.Our findings demonstrated that both vitamin forms significantly increased seedling growth at germination and early growth stages, especially at 50 ppm for pyridoxine and 100 ppm for thiamine. Pyridoxine at 50 ppm increased seedling length by approximately 35% compared to control, while thiamine at 100 ppm significantly promoted seedling fresh and dry wt by 4.36 and 1.36 g, respectively, compared to control seedling fresh wt 2.17 g and dry weight 1.07 g. Irrigation with 100 mM NaCl had a negative impact on plant growth and processes as well as the uptake of several critical ions, such as K+ and Mg+2, increasing Na uptake in comparison to that in control plants. Compared to control plants irrigated with NaCl solution, the photosynthetic pigments, soluble sugars, soluble proteins, and total antioxidant capacity increased in the presence of pyridoxine and thiamine, both at 50 and 100 ppm salinity. The proline content increased in both treated and untreated plants subjected to salt stress compared to that in control plants. Thiamine, especially at 50 ppm, was more effective than pyridoxine at improving plant health under saline conditions. An increase in Vicia faba plant tolerance to salinity was established by enhancing antioxidant capacity via foliar application of vitamin B through direct and indirect scavenging methods, which protect cell macromolecules from damage by oxidative stress, the highest antioxidant capacity value 28.14% was recorded at 50 ppm thiamine under salinity stress.The provided results is aguide for more researches in plant physiology and molecular biology to explain plant response to vitamins application and the suggest the sequence by which vitamins work inside plant cell.

Syngeneic Mouse Models for Pre-Clinical Evaluation of CAR T Cells.

Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies. Unfortunately, this improvement has yet to be translated into the solid tumor field. Current immunodeficient models used in pre-clinical testing often overestimate the efficacy of CAR T cell therapy as they fail to recapitulate the immunosuppressive tumor microenvironment characteristic of solid tumors. As CAR T cell monotherapy is unlikely to be curative for many solid tumors, combination therapies must be investigated, for example, stromal remodeling agents and immunomodulators. The evaluation of these combination therapies requires a fully immunocompetent mouse model in order to recapitulate the interaction between the host's immune system and the CAR T cells. This review will discuss the need for improved immunocompetent murine models for the pre-clinical evaluation of CAR T cells, the current use of such models and future directions.

A Case Report of Successful Live Pregnancy Following Embryo Transfer in a Thin Endometrium.

Managing a thin endometrium is a common challenge in assisted reproductive treatments. The thickness of the endometrium is crucial for embryo implantation, with younger patients generally having higher success rates even with a thinner lining. A frozen embryo transfer cycle often allows for a more thorough assessment of the endometrium compared to a fresh transfer. We present a case of a 36-year-old woman who presented to our fertility center with primary infertility for six years. Despite having regular menstrual cycles, her endometrial thickness consistently measured between 5 and 6.0 mm on ultrasonography. She underwent ovarian stimulation using an antagonist protocol, resulting in the retrieval of oocytes and the freezing of three embryos. However, three frozen embryo transfer cycles were cancelled due to inadequate endometrial thickness (ranging from 4.3 to 5.2 mm). In the fourth cycle, she was treated with gonadotropins with the goal of achieving two to three follicles and improved endometrial thickness. Triggering was performed on day 15, followed by the transfer of one frozen embryo at an endometrial thickness of 5.7 mm. Her beta-human chorionic gonadotropin (hCG) level was positive, with an initial value of 136.9 mIU/mL, and she subsequently delivered a healthy baby. This case highlights the challenges of managing a thin endometrium in assisted reproductive techniques. Through persistent efforts and tailored treatment protocols, a successful live birth was achieved despite recurrent thin endometrium. This case underscores the importance of individualized treatment strategies in overcoming endometrial challenges in infertility treatments.

Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model.

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC0 - 24 and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

NSAIDs between past and present; a long journey towards an ideal COX-2 inhibitor lead.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most abundantly used classes among therapeutic agents in medicine. NSAIDs inhibit the enzyme cyclooxygenase (COX), which is responsible for the conversion of arachidonic acid to prostaglandins. Meanwhile, non-selective NSAIDs are considered as a double-edged weapon since inhibition of COX-1 can lead to gastrointestinal side effects and kidney damage, whereas selective COX-2 inhibition provides anti-inflammatory effects without gastrointestinal toxicity. The detection of COX-2 role in inflammation process launched a new era in its management. Several trials have been established to proceed towards selectivity of well-defined anti-inflammatory members. COX-2 selective inhibitors are evidently safer on the gastrointestinal tract than non-selective NSAIDs. Nevertheless, their unexpected cardiovascular risks cannot be ignored. This review article highlights the latest trials aimed at developing new compounds with promising selective COX-2 activity.

Design, synthesis, biological evaluation, and docking studies of novel triazolo[4,3-b]pyridazine derivatives as dual c-Met/Pim-1 potential inhibitors with antitumor activity.

Interest has been piqued in c-Met and Pim-1, potential new cancer treatment targets. A variety of triazolo[4,3-b]pyridazine derivatives were synthesized to create powerful dual c-Met/Pim-1 inhibitors having the pharmacophoric elements of both enzyme inhibitors. All derivatives were screened for their cytotoxic effects on 60 cancer cell lines. Compounds 4g and 4a, had strong antiproliferative cytotoxic impacts on tumor cells, with mean GI% values of 55.84 and 29.08%, respectively. Research revealed that 4g has more powerful inhibitory activity against c-Met and Pim-1, with IC50 of 0.163 ± 0.01 and 0.283 ± 0.01 µM, respectively than the reference and derivative 4a. Moreover, compound 4g was the subject of an additional investigation into biological processes. The findings showed that compound 4g caused MCF-7 cells to arrest in the S stage of the cell cycle. Also, it accelerated the progress of apoptosis 29.61-fold more than the control. Compound 4g demonstrated a significantly higher level of caspase-9 and a decreased level of p-PI3K, p-AKT, and p-mTOR compared to staurosporine. Later, analysis of 4g showed good drug-ability and pharmacokinetic properties. A similar mode of interaction at the ATP-binding site of c-Met and Pim-1 compared to the docked ligands was suggested by additional docking studies of compound 4g.

Mapping Biomaterial Complexity by Machine Learning.

Biomaterials often have subtle properties that ultimately drive their bespoke performance. Given this nuanced structure-function behavior, the standard scientific approach of one experiment at a time or design of experiment methods is largely inefficient for the discovery of complex biomaterials. More recently, high-throughput experimentation coupled with machine learning methods has matured beyond expert users allowing scientists and engineers from diverse backgrounds to access these powerful data science tools. As a result, we now have the opportunity to strategically utilize all available data from high-throughput experiments to train efficacious models and map the structure-function behavior of biomaterials for their discovery. Herein, we discuss this necessary shift to data-driven determination of structure-function properties of biomaterials as we highlight how machine learning is leveraged in identifying physicochemical cues for biomaterials in tissue engineering, gene delivery, drug delivery, protein stabilization, and antifouling materials. We also discuss data-mining approaches that are coupled with machine learning to map biomaterial functions that reduce the load on experimental approaches for faster biomaterial discovery. Ultimately, harnessing the prowess of machine learning will lead to accelerated discovery and development of optimal biomaterial designs.

HERV-K np9 and HERV-R env: Two endogenous retrovirus products with potential Pathogenic roles in pediatric acute lymphoblastic leukemia.

OBJECTIVES: Human endogenous retroviruses (HERVs) are integral components of the human genome, and their reactivation has been implicated in the pathogenesis of some malignancies. External viral co-infections are suspected to play a role in HERV transactivation. This study aimed to investigate the expression of HERV-K np9 elements and HERV-R env gene in pediatric acute lymphoblastic leukemia (ALL) patients. Additionally, we explored potential correlations between HERV expression and common viral infections prevalent in this group of patients. METHODS: Blood samples were collected from 43 pediatric ALL patients and 48 age- and sex-matched healthy controls. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of HERV-K np9 and HERV-R env, along with herpes simplex virus (HSV), parvovirus B19, and polyomavirus BK. RESULTS: HERV-K np9 and HERV-R env showed significantly higher expression in the peripheral blood of ALL patients compared to healthy controls (p < .001 and p = .003, respectively). HSV positivity was associated with significantly increased HERV-K np9 expression. No significant correlations were observed between other investigated viruses and HERV gene expression. CONCLUSION: The overexpression of HERV-K np9 and HERV-R env in pediatric ALL patients suggest their potential role in leukemogenesis. Our findings also suggest a possible link between HSV infection and HERV reactivation in this population. Future investigations are needed to understand the precise roles of these genes and viral infections in the development of ALL.

Socioeconomic disparities and their effect on medical student academic attainment sudanese universities.

BACKGROUND: Socioeconomic status (SES) is a social classification factor that takes into account income, parental education and occupation. SES has been shown to play an important role in shaping students' academic performance, including in medical schools, but there still remains significant variation in findings around SES and academic achievement worldwide. We aim to assess and explore socioeconomic disparities and their effects on medical school performance at Sudanese public and private universities. OBJECTIVES: The objective of our study was to assess the effects of age, sex, living conditions, parental education and income level on the academic achievement of medical students from universities in Sudan. METHODS: This cross-sectional study was conducted among undergraduate medical students at ten public universities in Sudan between September and December 2023. Participants were included if they were older than 18 years and were studying in their 2nd year or older. The data were collected using an online questionnaire with open- and closed-ended questions measuring age, living conditions, parental income level and education. A convenience sampling method was used to recruit participants from universities. The data were analyzed using SPSS v28.0.0, and a p value less than 0.05 was used to indicate statistical significance. RESULTS: We received 832 responses, 516 (62%) from females and 307 (36.9%) from males. The median age was 23 years. Most students lived with their families (61.1%), followed by student housing (28.2%). This study revealed age (p = .024) (95% Cl: 0.025- 0.023) andhigh family income (p = .019) (95% Cl: 0.018- 0.02) are associated with academic achievement in the long term, as demonstrated through cumulative grade point average (cGPA). CONCLUSION: The findings underscore the importance of targeted support systems to bridge the socioeconomic gaps that exist among medical students, allowing all students to thrive academically regardless of their background. CLINICAL TRIAL NUMBER: None.

Synthesis, COX-2 inhibition, anti-inflammatory activity, molecular docking, and histopathological studies of new pyridazine derivatives.

Five new pyridazine scaffolds were synthesized and assessed for their inhibitory potential against both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) compared with indomethacin and celecoxib. The majority of the synthesized compounds demonstrated a definite preference for COX-2 over COX-1 inhibition. Compounds 4c and 6b exhibited enhanced potency towards COX-2 enzyme with IC50 values of 0.26 and 0.18 µM, respectively, compared to celecoxib with IC50 = 0.35 µM. The selectivity index (SI) of compound 6b was 6.33, more than that of indomethacin (SI = 0.50), indicating the most predominant COX-2 inhibitory activity. Consequently, the in vivo anti-inflammatory activity of compound 6b was comparable to that of indomethacin and celecoxib and no ulcerative effect was detected upon the oral administration of compound 6b, as indicated by the histopathological examination. Moreover, compound 6b decreased serum plasma PEG2 and IL-1ß. To rationalize the selectivity and potency of COX-2 inhibition, a molecular docking study of compound 6b into the COX-2 active site was carried out. The COX-2 inhibition and selectivity of compound 6b can be attributed to its ability to enter the side pocket of the COX-2 enzyme and interact with the essential amino acid His90. Together, these findings suggested that compound 6b is a promising lead for the possible design of COX-2 inhibitors that could be employed as safe and effective anti-inflammatory drugs.

Naturally based pyrazoline derivatives as aminopeptidase N, VEGFR2 and MMP9 inhibitors: design, synthesis and molecular modeling.

Aminopeptidase N (APN) is regarded as an attractive target for cancer treatment due to its overexpression in various types of malignancies and its close association with cancer angiogenesis, metastasis and invasion. Herein the authors describe the design, synthesis and biological evaluation of some naturally based pyrazoline derivatives. Among these compounds, the diphenylpyrazole carbothioamide 8 showed significant activity and selectivity index (SI = 4.7) on breast (MCF-7) human cancer cell line and was capable of inhibiting APN with pIC50 value of 4.8, comparable to the reference standard. Further evaluation of derivative 8 against VEGFR2 and MMP9 as biomarkers for angiogenesis and invasion showed that the selected compound had an inhibitory activity on both proteins with pIC50 values of 6.7 and 6.4, respectively. Additionally, the migration ability of cells following treatment with the diphenylpyrazole derivative decreased to record a percentage wound closure of 57.77 for compound 8versus 97.03 for the control. The promising derivative arrested cell growth at the G1 phase inducing early and late apoptosis. Finally, docking and ADMET in silico studies were performed.

Optimized scleroglucan production by Athelia rolfsii and in vitro Sclg-5-fluorouracil release investigations.

Scleroglucan is a notable member of the ß-glucan microbial polysaccharides with a long tradition of industrial and therapeutic use. The local strain, previously identified as Athelia rolfsii TEMG MH 236106 produced an appreciable amount of scleroglucan using glucose as a carbon source and yeast extract as a nitrogen source. Plackett-Burman design was employed to effectively screen critical medium composition, culture, and fermentation conditions. Athelia rolfsii TEMG MH 236106 produced the maximum amount of scleroglucan (18.12 g/L) with a 45.3 % glucose conversion. Out of the eleven variables, the most effective factors showing a high level of significance are as follows: glucose, yeast extract, citric acid, inoculum disc numbers, culture volume and incubation time. An update to maximize scleroglucan production in the central composite design for four parameters (glucose and yeast extract concentrations, disc number, medium volume and incubation time) with 31 runs was applied and the production of scleroglucan reached its maximum at 31.56 g/L with 78.9 % glucose conversion. Three models of Sclg-5-fluorouracil complexes have been employed to study in vitro drug release investigations. Hence, the Sclg-5-FU (5 and 10 mg/mL) models appeared to be the most suitable for drug administration due to their concentration and distribution within capsules.

Remdesivir ameliorates ulcerative colitis-propelled cell inflammation and pyroptosis in acetic acid rats by restoring SIRT6/FoxC1 pathway.

INTRODUCTION: Ulcerative colitis (UC) is a primary culprit of inflammatory bowel disease that entails prompt and effective clinical intervention. Remdesivir (RDV), a broad-spectrum antiviral nucleotide, has been found to exert anti-inflammatory effects in experimental animals. AIM: This study investigates the prospective anti-inflammatory merit of RDV on an experimental model of UC. The role of SIRT6/FoxC1 in regulating colonic cell inflammation and pyroptosis is delineated. METHOD: Rats were challenged with a single intrarectal dose of acetic acid (AA) solution (2 ml; 4 % v/v) to induce colitis. RDV (20 mg/kg, ip) and sulfasalazine (100 mg/kg, po) were administered to rats 14 days before the injection of AA. RESULTS: Administration of RDV ameliorated colonic cell injury and loss as manifested by improvement of severe colon histopathological mutilation and macroscopic damage and disease activity index scores together with restoration of normal colon weight/length ratio. In addition, RDV alleviated colonic inflammatory reactions, thereby curtailing NF-κB activation and the inflammatory cytokines, TNF-α, IL-18, and IL-1ß. Mitigation of colonic oxidative stress and apoptotic reactions were also evident in the setting of RDV treatment. Mechanistically, RDV enhanced the anti-inflammatory cascade, SIRT6/FoxC1, together with curbing the pyroptotic signal, NLRP3/cleaved caspase-1/Gasdermin D-elicited colonic inflammatory cell death. CONCLUSION: This study reveals, for the first time, the anti-inflammatory effect of RDV against experimental UC. Augmenting SIRT6/FoxC1-mediated repression of colonic inflammation and pyroptosis might advocate the colo-protective potential of RDV.

Pharmacokinetic assessment of low dose decitabine in combination therapies: Development and validation of a sensitive UHPLC-MS/MS method for murine plasma analysis.

Decitabine is a DNA methyltransferase inhibitor used in the treatment of acute myeloid leukemia and myelodysplastic syndrome. The notion that ongoing trials are presently exploring the combined use of decitabine, with or without the cytidine deaminase inhibitor cedazuridine, and other antileukemic drugs necessitates a comprehensive understanding of pharmacokinetic properties and an evaluation of drug-drug interaction liabilities. We report here the development and validation of a sensitive UHPLC-MS/MS method for quantifying decitabine in mouse plasma, which should be useful for such studies. The method involved a one-step protein precipitation extraction, and chromatographic separation on an XBridge HILIC column using gradient elution. The method was found to be robust, accurate, precise, and sufficiently sensitive (lower limit of quantitation, 0.4 ng/mL) to determine decitabine concentrations in microvolumes of plasma from mice receiving the agent orally or intravenously in the presence or absence of cedazuridine.

Influence of selected non-antibiotic pharmaceuticals on antibiotic resistance gene transfer in Escherichia coli.

BACKGROUND: Antibiotic resistance genes (ARGs) transfer rapidly among bacterial species all over the world contributing to the aggravation of antibiotic resistance crisis. Antibiotics at sub-inhibitory concentration induce horizontal gene transfer (HRT) between bacteria, especially through conjugation. The role of common non-antibiotic pharmaceuticals in the market in disseminating antibiotic resistance is not well studied. OBJECTIVES: In this work, we indicated the effect of some commonly used non-antibiotic pharmaceuticals including antiemetic (metoclopramide HCl) and antispasmodics (hyoscine butyl bromide and tiemonium methyl sulfate) on the plasmid-mediated conjugal transfer of antibiotic resistance genes between pathogenic E. coli in the gastric intestinal tract (GIT). METHODS: Broth microdilution assay was used to test the antibacterial activity of the tested non-antibiotic pharmaceuticals. A conjugation mating system was applied in presence of the studied non-antibiotic pharmaceuticals to test their effect on conjugal transfer frequency. Plasmid extraction and PCR were performed to confirm the conjugation process. Transmission electron microscopy (TEM) was used for imaging the effect of non-antibiotic pharmaceuticals on bacterial cells. RESULTS: No antibacterial activity was reported for the used non-antibiotic pharmaceuticals. Plasmid-mediated conjugal transfer between isolates was induced by metoclopramide HCl but suppressed by hyoscine butyl bromide. Tiemonium methylsulfate slightly promoted conjugal transfer. Aggregation between cells and periplasmic bridges was clear in the case of metoclopramide HCl while in presence of hyoscine butyl bromide little affinity was observed. CONCLUSION: This study indicates the contribution of non-antibiotic pharmaceuticals to the dissemination and evolution of antibiotic resistance at the community level. Metoclopramide HCl showed an important role in the spread of antibiotic resistance.

Effect of treatment of chronic hepatitis c virus patients with direct-acting anti-retroviral drugs on semen and hormonal parameters.

Objective: Hepatitis C virus (HCV) infection is known to influence the seminal and hormonal parameters of infected men. This study was performed to assess the effects of HCV clearance using direct-acting antiviral (DAA) agents on semen and hormonal parameters. Methods: A total of 50 patients with chronic HCV were enrolled, and conventional semen analysis was performed according to World Health Organization guidelines. Basal levels of total testosterone, free testosterone (FT), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin, and sex hormone-binding globulin (SHBG) were assessed before and 3 months after treatment with DAAs. Results: Following DAA treatment, statistically significant increases were observed in sperm motility and the proportion of grade A sperm. Additionally, the percentage of abnormal forms was significantly decreased after treatment (p=0.000). However, no significant differences were observed in semen volume, concentration, or total sperm count. Sex hormone analysis of patients after DAA treatment revealed significant increases in FT, LH, and FSH levels, along with significant decreases in SHBG, prolactin, and E2 levels. Conclusion: Following HCV clearance, we noted an improvement in sperm motility and an increase in the percentage of sperm with normal morphology. Treatment with DAAs was also associated with increased levels of FT and LH, along with decreased levels of SHBG, prolactin, and E2.

Efficacy and safety of etrolizumab in treatment of moderate to severe ulcerative colitis: A systematic review and meta-analysis.

Background: Etrolizumab is a promising drug for treating moderate to severe ulcerative colitis. Aim: The aim of this study was to assess the efficacy and safety of etrolizumab for induction and maintenance of remission in moderate to severe ulcerative colitis. Methods: We searched the following databases: PUBMED, Web of Science, OVID, and SCOPUS from inception to January 15. Inclusion criteria were any phase 2 and 3 clinical trials that compared etrolizumab with a placebo in treating moderate to severe ulcerative colitis, excluding case reports, animal studies, phase 1 trials, and conference abstracts due to duplication. We used RevMan software (5.4) for the meta-analysis. Results: Five clinical trials were included in our meta-analysis. The total number of patients included in the study is 1248 patients, 860 patients in the etrolizumab group and 388 patients in the placebo group. In the induction phase, the pooled analyses showed a statistically significant association between etrolizumab and increased clinical remission, and endoscopic remission compared with placebo (risk ratio [RR] = 2.66, 95% confidence interval [CI] = 1.69-4.19, p < 0.0001), and (RR = 2.35, 95% CI = 1.52-3.65, p = 0.0001), respectively. In the maintenance phase, the pooled analyses showed a statistically significant association between etrolizumab and increased histologic remission and endoscopic remission (RR = 2.04, 95% CI = 1.40-2.98, p = 0.0002) and (RR = 1.92, 95% CI = 1.29-2.85, p = 0.001), respectively. No statistically significant difference was observed in adverse events between etrolizumab and placebo in the induction and maintenance phases. Conclusion: Our results show that etrolizumab is an effective and safe drug for the induction and maintenance of clinical remission in moderate to severe ulcerative colitis patients, as proved by histologic and endoscopic findings. Future randomized trials are still needed to compare etrolizumab to the other agents and further establish its value for the practice.

Exploring the Heart Failure Connection in Long COVID Patients: A Narrative Review.

In this narrative review, we explore the relationship between long COVID patients and their risk of developing heart failure (HF). Patients with long COVID face a heightened risk of HF, a critical cardiovascular complication linked to the prolonged effects of COVID-19. Clinical manifestations of long COVID-associated HF present diagnostic challenges, complicating patient management. Multidisciplinary care is essential to address these complexities effectively. We found that long COVID can result in various cardiovascular issues including HF. The current view is long COVID leads to HF by activating systemic inflammation by causing endothelial dysfunction, which leads to activation of the complement pathways, tissue factor pathways, and Von Willebrand factor; activation of all these factors leads to venous and arterial thrombosis, which could lead to clogging of blood vessel of the heart leading to cardiovascular complications. The association between long COVID and HF can be challenging despite being recognized as comorbidity because biomarkers are not dependable in determining whether a patient had HF before or after contracting COVID-19. Emerging therapeutic modalities offer hope for improving outcomes, but further research is needed to refine management strategies and mitigate long-term cardiovascular consequences of COVID-19.