Arthroscopic Assessment of the Incidence of Biceps Pulley Lesions Associated With Rotator Cuff Tears: An Observational Study.

The shoulder joint houses a stabilizing structure called the biceps pulley. Biceps pulley lesions can trigger anterior shoulder pain and frequently coincide with rotator cuff tears, whose prevalence rises with age. In our study, we aim to assess the incidence of biceps pulley lesions associated with rotator cuff tears in patients undergoing arthroscopic repair, the possible associated factors, and whether MRI findings were correlated with them. This study was a prospective observational one conducted at Al-Hadra University Hospital. The patients aged 40 to 65 years were indicated for arthroscopic repair of a rotator cuff tear. We used IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. to conduct the analysis. A total of 60 patients were enrolled in the study. The mean age was 50.97 ± 6.90. The overall incidence of biceps pulley lesions was 85%. Older age was found to be significantly associated with increased incidence. On the other hand, gender, and the mode of injury (cuff tear) had no significant associations with the incidence. Also, formal MR had no significance in diagnosing biceps pulley lesions. The overall incidence of biceps pulley lesions in the current study was 85%. The older the patient with a cuff tear, the greater the incidence of finding a pulley lesion arthroscopically. Moreover, MRI did not have a significant role in diagnosing the biceps pulley lesions.

Outcomes of Non-vascularized Fibular Grafts in Proximal Humerus Aneurysmal Bone Cysts.

Introduction This study focuses on the management of primary aneurysmal bone cysts (ABCs) through comprehensive curettage, hydrogen peroxide lavage, and non-vascularized strut fibular grafting. Methods The research encompassed 20 cases, predominantly males (80%), with an average age of 11.35 years. Patient assessment involved thorough history-taking, clinical examinations, and radiological evaluations, including plain radiographs, CT scans, and MRI. The study evaluated healing, bone consolidation, and complications, with patients assessed using the Musculoskeletal Tumor Society (MSTS) upper limb score. Results and discussion The results demonstrated a mean MSTS score of 91.55%, indicating favorable outcomes compared to prior studies. The utilization of non-vascularized autogenous fibular grafts offered effective mechanical stabilization and facilitated an early return to normal function, even prior to complete cavity filling. Our research underscores the efficacy of this treatment approach for primary ABC, particularly in achieving satisfactory functional outcomes. Moreover, the findings contribute to the understanding of optimal management strategies for ABC, considering factors such as patient age, lesion location, vascularity, and size. Conclusion The study advocates for the adoption of thorough curettage, hydrogen peroxide lavage, and non-vascularized strut fibular grafting as a reliable treatment modality for primary ABC. This approach highlights its potential to enhance patient outcomes and functional recovery.

Treatment Outcomes in Vertical Shear Pelvic Fractures: A Comparative Study.

Background Vertical shear (VS) pelvic ring injuries present a unique challenge due to their inherent vertical and rotational instability and the risk of massive bleeding. VS injuries may result from either bony or ligamentous injury. The goal in the treatment of VS fractures of the pelvis is to achieve and maintain an accurate reduction of the displaced hemipelvis. Aim of the study This study aimed to compare the results of the treatment of VS fractures pelvis by using iliosacral (IS) screws versus lumbopelvic fixation (LPF). Methodology This retrospective study was carried out on 40 patients with VS fracture pelvis injuries at El Hadara University Hospital, Alexandria, Egypt, from January 2020 to December 2020. Twenty of them were treated by an IS screw, and the other 20 were treated by LPF. Then, both groups were followed up for six months with regard to union rate, metal failure, and clinical outcomes. Results The EQ-5D showed a significant improvement in LPF more than the IS screw group in the five items of the score. Moreover, the total EQ-5D index showed a significant increase in the LPF group more than the IS screw group (p < 0.05). The incidence of neurological complication was found in four cases in the IS screw group, while no cases were found in the LPF group. The infection was found in six patients in the IS screw group and only three cases in the LPF group. The malunion was found in two cases in the IS screw group and no cases in the LPF group. The neurological change and the incidence of infection were significantly higher in the IS screw group than in the LPF group (p < 0.05). Conclusion Our results demonstrate reliable maintenance of reduction and acceptable complication rates with a minimally invasive LPF for VS fractured pelvis. The benefits of minimally invasive LPF may be offset by increased elective reoperations for the removal of instrumentation.

The role of the community pharmacy work system in the enactment of pharmacists' non-technical skills.

Non-technical skills are recognised as important in various work domains, but have been the subject of debate regarding their role in ergonomics/human factors, given their focus on human behaviour itself rather than the interaction between people and systems. This study aimed to examine the relationship between non-technical skills and the work system in which they are enacted. The study setting was community pharmacies in England. Qualitative data were obtained from observation of seven pharmacists and semi-structured interviews with 16 pharmacists, and subjected to thematic analysis. Elements of their work system were found to be related to their non-technical skills; either by creating a need for the skill in the first place, or by facilitating or inhibiting its enactment. The findings highlight the importance of considering the work system that contextualises individuals' and teams' behaviour, in addition to the behaviour itself, when investigating non-technical skills.

The obvious focus of interventions to enhance non-technical skills is the behaviour of individuals and teams. However, we highlight the importance of considering the work system within which people are operating, as this forms the context within which non-technical skills are exercised. We suggest particular ways in which the work system might influence the exercise of non-technical skills.

The peels of sacred Lotus (Nelumbo nucifera) rhizomes suppress allergic reactions by inhibiting the A23187-induced degranulation in rat basophilic leukemia (RBL2H3) cells.

We isolated ten compounds from methanolic extract of the peels of sacred lotus (Nelumbo nucifera) rhizomes which were identified as ß-sitosterol linoleate 1, ß-sitosterol 2, lupeol 3, stigmasterol 3-O-ß-D-glucoside 4, oleanolic acid 5, betulinic acid 6, pinoresinol 7, 4-hydroxybenzoic acid 8, catechin 9 and gallocatechin 10. All of the isolated compounds from the peels of sacred lotus rhizomes are reported for the first time, and were investigated for their anti-allergic activity. We found that three of them, stigmasterol 3-O-ß-D-glucoside 4, oleanolic acid 5 and pinoresinol 7, were capable of inhibiting A23187-induced degranulation in RBL-2H3 cells with IC50 values 0.18 ± 0.01 mM, 0.28 ± 0.06 mM, and 0.27 ± 0.01 mM, respectively. With an exception to 4, compounds 5 and 7 achieved the anti-allergic effect without affecting the cells viability even at higher concentrations with their selectivity indices (SI) being >5. By reducing A23187-induced degranulation, it is suggestive of a mechanism attenuation of Ca2+ elevation. Our findings suggest that, the peels of sacred lotus rhizomes would be beneficial for providing an inexpensive source for the production of bioactive compounds with anti-allergic effect.

Crossover effect of knee and ankle joint training on knee mechanics after ACL reconstruction: A randomized controlled trial.

BACKGROUND: Anterior cruciate ligament (ACL) rehabilitation is a common intervention after ACL reconstruction. Since different types of exercise can influence muscle and kinematic parameters in diverse ways, the training order between the knee and ankle joints may also change gait parameters. PURPOSE: This study aimed to investigate whether the training sequence of the knee and ankle joints (knee followed by ankle training or vice-versa) in an ACL reconstruction (ACLR) rehabilitation program has any effects on knee extension and flexion torques. METHODS: Forty-two men (aged 20-30 years) with ACLR participated in this study. They were randomly allocated to receive one of two interventions: (A) knee joint training followed by ankle training or (B) ankle joint training followed by knee training. After five weeks (four weeks of intervention and one-week washout), participants crossed from one group to another for an additional four weeks. Knee extension and flexion torques were assessed during the stance phase of the gait cycle before and after the intervention program. RESULTS: Two-way Mixed-design MANOVA showed that knee extension torque improved significantly in both groups after training (p = 0.001, Cohen's D = 0.65), while the knee flexion torque increased significantly only in group B (p= 0.001, Cohen's D = 0.97). When comparing both groups, patients of group B presented significant improvements in the post-training mean values of all tested variables compared with group A. CONCLUSION: Starting a post-ACLR rehabilitation program with ankle training followed by knee training is better to improve knee flexion and extension torques during the stance phase of the gait cycle than starting the program by training the knee first, followed by the ankle. Future studies using a mixed-gender sample and different types of ACLR operations are necessary to examine whether similar improvements will happen as well as to test their effects on many sports activities.

A Comparison of the Results of Platelet-Rich Plasma Injection Versus the Results of Corticosteroid Injections in De-Quervain Tenosynovitis.

BACKGROUND:  De Quervain tenosynovitis (DQT) is a condition that affects the first extensor compartment of the wrist, resulting in stenosing tenosynovitis. This work aimed to evaluate the effects of platelet-rich plasma (PRP) injection in the treatment of DQT in comparison with corticosteroid (CS) injections. METHODS:  This study was carried out on 40 DQT patients aged above 18 years old of both sexes, based on a combination of clinical symptoms and signs including persistent tenderness on the radial styloid, swelling on the radial styloid, positive provocative tests such as the Finkelstein test, and patients with failed medical treatment. Patients were divided into two equal groups: group I and group II. Group I was injected with PRP, and group II was injected with CS. Follow-ups were conducted at two weeks and six months. RESULTS:  There were statistically significant differences among both groups regarding the visual analog scale (VAS), and Disabilities of Arm, Shoulder, and Hand (QuickDASH-9) score. However, complications were statistically insignificant between both groups. After injection, CS was better than PRP after two weeks, but PRP was superior to CS after six months concerning QuickDASH-9 and VAS. These differences were statistically significant. CONCLUSIONS:  CS is more effective than PRP in the short term (two weeks) and PRP is more effective in the intermediate term (six months). Both modalities are safe; however, PRP is relatively safer than CS.

Serum lncRNAs TUG1, H19, and NEAT1 and their target miR-29b/SLC3A1 axis as possible biomarkers of preeclampsia: Potential clinical insights.

To date, the epigenetic signature of preeclampsia (PE) is not completely deciphered. Oxidative stress-responsive long non-coding RNAs (lncRNAs) are deregulated in preeclamptic placenta; however, their circulating profiles and diagnostic abilities are still unexplored. We investigated serum redox-sensitive lncRNAs TUG1, H19, and NEAT1, and their target miR-29b/cystine/neutral/dibasic amino acids transporter solute carrier family 3, member 1 (SLC3A1) as potential non-invasive biomarkers of PE risk, onset, and severity. We recruited 82 patients with PE and 78 healthy pregnant women. We classified PE patients into early-onset (EOPE) and late-onset (LOPE) subgroups at a cut-off 34 gestational weeks and into severe and mild PE subgroups by blood pressure and proteinuria criteria. Bioinformatics analysis was employed to select lncRNAs/microRNA/target gene interactions. Serum H19, NEAT1, and SLC3A1 mRNA expression were reduced, meanwhile miR-29b levels were elevated, whereas there was no significant difference in TUG1 levels between PE patients and healthy pregnancies. Serum H19 levels were lower, whereas miR-29b levels were higher in EOPE versus LOPE. Serum miR-29b and H19 levels were higher in severe versus mild PE. ROC analysis identified serum H19, NEAT1, miR-29b, and SLC3A1 as potential diagnostic markers, with H19 (AUC = 0.818, 95%CI = 0.744-0.894) and miR-29b (AUC = 0.82, 95%CI = 0.755-0.885) were superior discriminators. Only H19 and miR-29b discriminated EOPE and severe PE cases. In multivariate logistic analysis, miR-29b and H19 were associated with EOPE, using maternal age and gestational age as covariates, while miR-29b was associated with severe PE, using maternal age as covariate. Studied markers were correlated with clinical and ultrasound data in the overall PE group. Serum H19 and TUG1 were negatively correlated with albuminuria in EOPE and LOPE, respectively. NEAT1 and SLC3A1 were correlated with ultrasound data in EOPE. Likewise, TUG1, miR-29b, and SLC3A1 showed significant correlations with ultrasound data in LOPE. Conclusively, this study configures SLC3A1 expression as a novel potential serum biomarker of PE and advocates serum H19 and miR-29b as biomarkers of EOPE and miR-29b as a biomarker of PE severity.

Targeting JAK2/STAT3, NLRP3/Caspase-1, and PK2/PKR2 Pathways with Arbutin Ameliorates Lead Acetate-Induced Testicular Injury in Rats.

The reproductive system of males is adversely impacted by lead (Pb), a toxic heavy metal. The present study examined arbutin, a promising hydroquinone glycoside, for its potential ameliorative impact against Pb-induced testicular impairment in rats. The testicular injury was induced by the intraperitoneal administration of Pb acetate (20 mg/kg/day) for 10 consecutive days. Thirty-six rats were divided into six experimental groups (n = 6 per group): control, control treated with oral arbutin (250 mg/kg), control treated with intraperitoneal arbutin (75 mg/kg), untreated Pb, Pb treated with oral arbutin, and Pb treated with intraperitoneal arbutin. The treatments were administered daily for 10 days. Arbutin was administered by the oral and intraperitoneal routes to compare the efficacy of both routes in mitigating Pb acetate-induced testicular dysfunction. The current data revealed that both oral and intraperitoneal administration of arbutin significantly enhanced serum testosterone and sperm count/motility, indicating the amelioration of testicular dysfunction. In tandem, both routes lowered testicular histopathological aberrations and Johnsen's damage scores. These favorable outcomes were driven by dampening testicular oxidative stress, evidenced by lowered lipid peroxidation and increased glutathione and catalase antioxidants. Moreover, arbutin lowered testicular p-JAK2 and p-STAT3 levels, confirming the inhibition of the JAK2/STAT3 pro-inflammatory pathway. In tandem, arbutin suppressed the testicular NLRP3/caspase-1/NF-B axis and augmented the cytoprotective PK2/PKR2 pathway. Notably, intraperitoneal arbutin at a lower dose prompted a more pronounced mitigation of Pb-induced testicular dysfunction compared to oral administration. In conclusion, arbutin ameliorates Pb-evoked testicular damage by stimulating testicular antioxidants and the PK2/PKR2 pathway and inhibiting the JAK2/STAT3 and NLRP3/caspase-1 pro-inflammatory pathways. Hence, arbutin may be used as an adjunct agent for mitigating Pb-induced testicular impairment.

Propolis attenuates diabetes-induced testicular injury by protecting against DNA damage and suppressing cellular stress.

Introduction: Propolis has a wide range of biological and pharmacological actions, including antioxidant properties-particularly its phenolic and flavonoid constituents-that could potentially protect the reproductive system from oxidative damage. Method: Four groups were allocated 40 male Wistar rats each. The vehicle was given to the first group's normal control rats negative control. The second, third, and fourth groups of diabetic rats were given vehicle (diabetic control) and propolis orally at 50 and 100 mg/kg, respectively, for 8 weeks. Diabetes was induced in rats via injection of nicotinamide and streptozotocin (STZ). Fasting blood glucose (FBG) and insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and semen analysis were assessed. In addition, assessments of serum reproductive hormones, including total testosterone (TTST), estradiol (E2), follicle-stimulating hormone luteinizing hormone (LH), and prolactin (PRL), were measured at the end of the study. Tissue total testosterone, E2, and dihydrotestosterone were also evaluated. Serum and tissue oxidative enzymes, including catalase (CAT), superoxide dismutase, and glutathione peroxidase activities, were examined, and malondialdehyde content was determined. The pancreatic and testicular tissues were histopathologically examined, and proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (Bcl-2) in testicular tissue were immunohistochemically analyzed. Testicular tissue was examined for DNA integrity using a comet assay. Results: Compared to the STZ-control group, propolis greatly decreased FBG levels and improved the glycemic status of diabetic rats. In comparison to the STZ-DC group, propolis increased the number of sperm cells and the percent of morphologically normal and viable sperm in male rats, improving their fertility. Propolis also restored the pancreatic islets, protected the testis from oxidative stress, and increased levels of reproductive hormones in the blood, especially testosterone. Moreover, propolis at high doses demonstrated a strong positive response for Bcl-2 and a negative expression of proliferating cell nuclear antigen in spermatogenic cells. Conclusion: The data obtained strongly indicate that STZ causes severe impairments to the testis whereas propolis, acting as an antioxidant, protects against the adverse effects of STZ on the testis.

Repurposing ezetimibe as a neuroprotective agent in a rotenone-induced Parkinson's disease model in rats: Role of AMPK/SIRT-1/PGC-1α signaling and autophagy.

As a severe neurological disorder, Parkinson's disease (PD) is distinguished by dopaminergic neuronal degeneration in the substantia nigra (SN), culminating in motor impairments. Several studies have shown that activation of the AMPK/SIRT1/PGC1α pathway contributes to an increase in mitochondrial biogenesis and is a promising candidate for the management of PD. Furthermore, turning on the AMPK/SIRT1/PGC1α pathway causes autophagy activation, which is fundamental for maintaining neuronal homeostasis. Interestingly, ezetimibe is an antihyperlipidemic agent that was recently reported to possess pleiotropic properties in neurology by triggering the phosphorylation and activation of AMPK. Thus, our study aimed to investigate the neuroprotective potential of ezetimibe in rats with rotenone-induced PD by activating AMPK. Adult male Wistar rats received rotenone (1.5 mg/kg, s.c.) every other day for 21 days to induce experimental PD. Rats were treated with ezetimibe (5 mg/kg/day, i.p.) 1 h before rotenone. Ezetimibe ameliorated the motor impairments in open field, rotarod and grip strength tests, restored striatal dopamine and tyrosine hydroxylase in the SN, up-regulated p-AMPK, SIRT1, and PGC1α striatal expression, upsurged the expression of ULK1, beclin1, and LC3II/I, reduced Bax/Bcl2 ratio, and alleviated rotenone-induced histopathological changes in striatum and SN. Our findings also verified the contribution of AMPK activation to the neuroprotective effect of ezetimibe by using the AMPK inhibitor dorsomorphin. Together, this work revealed that ezetimibe exerts a neuroprotective impact in rotenone-induced PD by activating AMPK/SIRT-1/PGC-1α signaling, enhancing autophagy, and attenuating apoptosis. Thus, ezetimibe's activation of AMPK could hold significant therapeutic promise for PD management.

Activation of AMPK/mTOR-Driven Autophagy and Suppression of the HMGB1/TLR4 Pathway with Pentoxifylline Attenuates Doxorubicin-Induced Hepatic Injury in Rats.

Despite being an effective chemotherapeutic agent, the clinical use of doxorubicin (DOX) is limited by several organ toxicities including hepatic injury. Pentoxifylline (PTX) is a methylxanthine derivative with marked anti-inflammatory and anti-apoptotic features. It is unknown, however, whether PTX can mitigate DOX-evoked hepatotoxicity. This study aims to explore the potential hepatoprotective impact of PTX in DOX-induced hepatic injury and the underlying molecular mechanisms. Histopathology, immunohistochemistry, and ELISA were used to examine liver tissues. The current findings revealed that PTX administration to DOX-intoxicated rats mitigated the pathological manifestations of hepatic injury, reduced microscopical damage scores, and improved serum ALT and AST markers, revealing restored hepatic cellular integrity. These favorable effects were attributed to PTX's ability to mitigate inflammation by reducing hepatic IL-1ß and TNF-α levels and suppressing the pro-inflammatory HMGB1/TLR4/NF-κB axis. Moreover, PTX curtailed the hepatic apoptotic abnormalities by suppressing caspase 3 activity and lowering the Bax/Bcl-2 ratio. In tandem, PTX improved the defective autophagy events by lowering hepatic SQSTM-1/p62 accumulation and enhancing the AMPK/mTOR pathway, favoring autophagy and hepatic cell preservation. Together, for the first time, our findings demonstrate the ameliorative effect of PTX against DOX-evoked hepatotoxicity by dampening the hepatic HMGB1/TLR4/NF-κB pro-inflammatory axis and augmenting hepatic AMPK/mTOR-driven autophagy. Thus, PTX could be utilized as an adjunct agent with DOX regimens to mitigate DOX-induced hepatic injury.

Understanding migraine in Saudi society: An assessment of public knowledge and attitudes: A cross-sectional study.

OBJECTIVE: This study aims to assess the knowledge and perceptions of the public toward migraine in Saudi Arabia. METHODS: This cross-sectional survey assessed the knowledge and perceptions of migraine among Saudi Arabian individuals. The study was conducted over three months in 2023 (1st of June 2023 to 31st of August 2023) using a prevalidated online questionnaire divided into four sections. RESULTS: A total of 1,975 adults aged between 18 and 64 completed the web-based survey. Of these, over half were male (n = 1,268; 64.2%). The main causes of migraine identified by the participants were genetic disease (n = 540, 27.3%), followed by physical disease (n = 341, 17.3%), head trauma (n = 274, 13.9%), and psychiatric disease (n = 157, 7.9%). The main symptoms identified by the participants were photophobia (21%), followed by inability to control urine (14.1%), vomiting and nausea (13.8%), and vision loss (8.3%). The majority of the participants in this study had a good knowledge of migraines, while 49% had poor knowledge. The migraine knowledge score was significantly associated with the participants' gender (p = 0.002), age (p = 0.0001), educational level (p = 0.001), employment status (p = 0.001), monthly income (p = 0.0001), region (p = 0.0001), and history of migraine (p = 0.0001). CONCLUSION: Although one-third of the participants exhibiting good knowledge, deficiencies existed in certain clinical aspects, emphasizing the need for targeted educational interventions to enhance public awareness and understanding of migraines.

Targeting inflammation in glioblastoma: An updated review from pathophysiology to novel therapeutic approaches.

Glioblastoma (GBM) is a highly aggressive primary malignant brain tumor with a dismal prognosis despite current treatment strategies. Inflammation plays an essential role in GBM pathophysiology, contributing to tumor growth, invasion, immunosuppression, and angiogenesis. As a result, pharmacological intervention with anti-inflammatory drugs has been used as a potential approach for the management of GBM. To provide an overview of the current understanding of GBM pathophysiology, potential therapeutic applications of anti-inflammatory drugs in GBM, conventional treatments of glioblastoma and emerging therapeutic approaches currently under investigation. A narrative review was carried out, scanning publications from 2000 to 2023 on PubMed and Google Scholar. The search was not guided by a set research question or a specific search method but rather focused on the area of interest. Conventional treatments such as surgery, radiotherapy, and chemotherapy have shown some benefits, but their effectiveness is limited by various factors such as tumor heterogeneity and resistance.

Exploring the potential of Aspergillus wentii: secondary metabolites and biological properties.

Fungi are of considerable importance due to their capacity to biosynthesize various secondary metabolites with bioactive properties that draw high attention in new drug discovery with beneficial uses for improving human well-being and life quality. Aspergillus genus members are widespread and cosmopolitan species with varying economic significance in the fields of industry, medicine, and agriculture. Its species are renowned for their biosynthesis of secondary metabolites, characterized by both potent biological activity and structural novelty, making them a substantial reservoir for the development of new pharmaceuticals. The current work aimed at focusing on one species of this genus, Aspergillus wentii Wehmer, including its reported secondary metabolites in the period from 1951 to November 2023. A total of 97 compounds, including nitro-compounds, terpenoids, anthraquinones, xanthones, benzamides, and glucans. A summary of their bioactivities, as well as their biosynthesis was highlighted. Additionally, the reported applications of this fungus and its enzymes have been discussed. This review offers a useful reference that can direct future research into this fungus and its active metabolites, as well as their possible pharmacological and biotechnological applications.

Quillaja saponin mitigates methotrexate-provoked renal injury; insight into Nrf-2/Keap-1 pathway modulation with suppression of oxidative stress and inflammation.

BACKGROUND: Methotrexate (MTX) is an antineoplastic/immunosuppressive drug, whose clinical use is impeded owing to its serious adverse effects; one of which is acute kidney injury (AKI). Most of MTX complications emerged from the provoked pro-oxidant-, pro-inflammatory- and pro-apoptotic effects. Quillaja saponaria bark saponin (QBS) is a bioactive triterpene that has been traditionally used as an antitussive, anti-inflammatory supplement, and to boost the immune system due to its potent antioxidant- and anti-inflammatory activities. However, the protective/therapeutic potential of QBS against AKI has not been previously evaluated. This study aimed to assess the modulatory effect of QBS on MTX-induced reno-toxicity. METHODS: Thirty-two male rats were divided into 4-groups. Control rats received oral saline (group-I). In group-II, rats administered QBS orally for 10-days. In group-III, rats were injected with single i.p. MTX (20 mg/kg) on day-5. Rats in group-IV received QBS and MTX. Serum BUN/creatinine levels were measured, as kidney-damage-indicating biomarkers. Renal malondialdehyde (MDA), reduced-glutathione (GSH) and nitric-oxide (NOx) were determined, as oxidative-stress indices. Renal expression of TNF-α protein and Nrf-2/Keap-1 mRNAs were evaluated as regulators of inflammation. Renal Bcl-2/cleaved caspase-3 immunoreactivities were evaluated as apoptosis indicators. RESULTS: Exaggerated kidney injury upon MTX treatment was evidenced histologically and biochemically. QBS attenuated MTX-mediated renal degeneration, oxidant-burden enhancement, excessive inflammation, and proapoptotic induction. Histopathological analysis further confirmed the reno-protective microenvironment rendered by QBS. CONCLUSIONS: In conclusion, our results suggest the prophylactic and/or therapeutic effects of QBS in treating MTX-induced AKI. Such reno-protection is most-likely mediated via Nrf-2 induction that interferes with oxidant load, inflammatory pathways, and proapoptotic signaling.

Knowledge, Perception, and Self-Confidence of Antibiotic Resistance, Appropriate Antibiotic Therapy, and Antibiotic Stewardship Among Undergraduate Pharmacy Students in Sudan.

Background: Adequate training in infectious diseases and antibiotic resistance is crucial for pharmacy students to participate in antibiotic stewardship programs and understand microbiology careers. Aim: The study was carried out to assess the knowledge and self-reported confidence in antibiotic resistance, antibiotic therapy, and antimicrobial stewardship (AMS) among final-year undergraduate pharmacy students in Sudan. Methods: A cross-sectional study was conducted in three universities using a 57-item online questionnaire between April and May 2022. Results: A total of 109 students (response rate 36%) participated and showed average knowledge scores of 5.6±1.7 (out of 10.0) for antibiotic resistance, 4.9±2.0 (out of 5.0) for appropriate antibiotic therapy, and 3.1±1.4 (out of 5.0) for AMS. No significant differences were observed among schools. Some students reported poor knowledge about antibiotic therapy and the consequences of resistance. One-third of students lacked confidence in interpreting microbiological results. Knowledge of antibiotic resistance among students' practice area after graduation was higher (p=0.017) and those interested in ID careers (5.8 vs 4.8) (p=0.037). Male students (5.6 vs 4.5) and those interested in ID careers (4.3 vs 3.4) (p<0.001) had higher scores of appropriate antibiotic therapy. Students attended antibiotic resistance courses (51.5 vs 45.2), and those interested in ID significantly had higher self-confidence (55.3 vs 45.8) (p=0.008). Conclusion: Pharmacy students in Sudan have substantial knowledge of AMS and antibiotic resistance with poor knowledge of antibiotic therapy. Adequate training about infectious diseases and related topics is recommended to improve pharmacy students' understanding of microbiological findings, other competencies, and skills to incorporate in antimicrobial stewardship.

Integrating computational methods guided the discovery of phytochemicals as potential Pin1 inhibitors for cancer: pharmacophore modeling, molecular docking, MM-GBSA calculations and molecular dynamics studies.

Pin1 is a pivotal player in interactions with a diverse array of phosphorylated proteins closely linked to critical processes such as carcinogenesis and tumor suppression. Its axial role in cancer initiation and progression, coupled with its overexpression and activation in various cancers render it a potential candidate for the development of targeted therapeutics. While several known Pin1 inhibitors possess favorable enzymatic profiles, their cellular efficacy often falls short. Consequently, the pursuit of novel Pin1 inhibitors has gained considerable attention in the field of medicinal chemistry. In this study, we employed the Phase tool from Schrödinger to construct a structure-based pharmacophore model. Subsequently, 449,008 natural products (NPs) from the SN3 database underwent screening to identify compounds sharing pharmacophoric features with the native ligand. This resulted in 650 compounds, which then underwent molecular docking and binding free energy calculations. Among them, SN0021307, SN0449787 and SN0079231 showed better docking scores with values of -9.891, -7.579 and -7.097 kcal/mol, respectively than the reference compound (-6.064 kcal/mol). Also, SN0021307, SN0449787 and SN0079231 exhibited lower free binding energies (-57.12, -49.81 and -46.05 kcal/mol, respectively) than the reference ligand (-37.75 kcal/mol). Based on these studies, SN0021307, SN0449787, and SN0079231 showed better binding affinity that the reference compound. Further the validation of these findings, molecular dynamics simulations confirmed the stability of the ligand-receptor complex for 100 ns with RMSD ranging from 0.6 to 1.8 Å. Based on these promising results, these three phytochemicals emerge as promising lead compounds warranting comprehensive biological screening in future investigations. These compounds hold great potential for further exploration regarding their efficacy and safety as Pin1 inhibitors, which could usher in new avenues for combating cancer.

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD. Methods: The terms "Non-alcoholic Fatty Liver Disease" and "NAFLD" were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review. Results: The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%. Conclusion: Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.

The Effect of Melatonin Supplement on High Arterial Blood Pressure: An Overview from Clinicaltrials.gov.

Background: Melatonin is a hormone produced by the pineal gland primarily at night. It has been suggested that melatonin may possess various cardiovascular benefits, including the potential to lower blood pressure. For this reason, we sought to identify and provide evidence of the effectiveness of melatonin on high arterial blood pressure in clinical trials. Methods: Using the search term "melatonin and hypertension", a search of the ClinicalTrials.gov database was performed on October 10th, 2023. I defined the exclusion and inclusion criteria to isolate appropriate clinical trials. Inclusion criteria for the search included hypertension that utilized melatonin as a treatment supplement; all non-related trials were omitted from the search. The data extractions, including study title, study type, study status, and intervention and outcome details, were compiled. Results: Of the 13 clinical trials identified, only three focused on examining the effects of melatonin. The study titles, enrollment numbers, conditions, statuses, interventions, and outcome measures have been explained in depth. Information gathered from these clinical trials will assist us in identifying the possible risks and benefits of melatonin with respect to high arterial blood pressure. Conclusion: Melatonin has been shown to be an effective treatment for lowering blood pressure. More research is required to fully establish the potential benefits and risks and highlight the mechanisms through which melatonin may influence blood pressure regulation.