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Objective: The aim of the study is to design N5-(1H-pyrazol-3-yl)-3H-benzo[d]imidazole-2,5-diamine derivatives and evaluate its anti-obesity activity., Materials and Methods: A few pyrazole-fused benzimidazole derivatives were designed as potential Pancreatic Lipase (PL) inhibitors. The designed N5-(1H-pyrazol-3-yl)-3H-benzo[d]imidazole-2,5-diamine derivatives have been screened using the Lipinski rule of five, ADMET analysis, acute toxicity prediction, and molecular docking. Later on, the derivatives which possess the most drug-likeness properties and displayed the most potent inhibition of the enzyme in molecular docking were synthesized. Then, in vitro enzyme assay was performed., Results: Orlistat used as the standard exhibited 91±1.68% inhibition of the enzyme, displayed binding affinity (BA) of only -4.5 kcal/mol with Pancreatic Lipase (PL), and made only one salt bridge attractive charge and carbon-hydrogen bond with ASP79 and TRP252, respectively. Compound 9 displayed the most potent activity (93±1.12% inhibition of P.L. and -9.5 kcal/mol BA). It has formed five conventional H- bonds with GLU253, ILE78, ASP79, PHE258, and one Pi-donor H- bond with ILE78. From the present investigation, we hereby reported (E)-N2-((naphthalene-1-yl)methylene)-N5-(1H-pyrazol-3-yl)-3H-benzo[d]imidazole-2,5-diamine as most potent PL inhibitor for the treatment of obesity, which can be further optimized by undergoing more studies using in vivo and in vitro models., Conclusions: (E)-N2-((naphthalene-1-yl)methylene)-N5-(1H-pyrazol-3-yl)-3H-benzo[d]imidazole-2,5-diamine as most potent PL inhibitor for the treatment of obesity which can be further optimized better using more in vivo and in vitro models. PL plays a critical role in digesting dietary fat. Therefore, PL inhibitors are verified as a potential therapy for treating obesity.

Objective: The aim of the study was to analyze if there was a link between chronic diseases, like cardiovascular disease (CVD) and osteoarthritis (OA), and obesity in the population of Saudi Arabia's Hail region., Materials and Methods: The study was conducted over 12 months using an observational cross-sectional survey on 172 patients from five clinics in Hail, Saudi Arabia. A total of 172 individuals with obesity (BMI ≥ 30) finally participated in this research. The study evaluated sociodemographic variables via an electronic questionnaire with voluntary participation., Results: The study found a 76% prevalence of joint pain and 77.9% prevalence of cardiovascular abnormalities. Patients with CVD were older (58±23 vs. 56±12 years) than those with OA. CVD cases were found in 42 (31.3%) males and 92 (68.7%) females, whereas OA cases were recognized in 24 (18.5%) males and 106 (81.5%) females. The occurrence of various CVDs among our participants was 43 (32%) for high cholesterol, 64 (48%) for hypertension, and 27 for both high cholesterol and hypertension (20%). Definite osteophytes were found in 28 of 24 male knees (14 right and 14 left knees) and 175 of 106 female knees (88 right knees and 87 left knees)., Conclusions: The prevalence of obesity in the Hail region has continued to be a risk factor for CVD and OA in 2019 and 2020. The Saudi population has shown a higher prevalence of radiographic evidence of OA of the knee and associated symptoms than western civilizations, and preventive interventions are desperately needed in order to minimize overweight and obesity.

Objective: The aim of the study was to analytically compare the therapeutic effect of the addition of diet modification and regular exercise to oral agents., Materials and Methods: This cross-sectional study surveyed 1248 participants via online and offline modes by employing a questionnaire about an individual's management of diabetes. Group 1 patients follow Single Approach Management for Type 2 Diabetes Mellitus (T2DM), while Group 2 and Group 3 patients follow Multi-Approach Management for T2DM. Based on the answers, the participants were classified into three groups. The diagnostic criteria of Diabetes Mellitus Type-2 in this study were done by determining morning Fasting Blood Sugar (FBS) and glycated Hemoglobin (HbA1c)., Results: The current study found 656 single oral agent users and 592 combination regimens users among all the study participants. The study also found that, among all participants, 511 patients were on mild to moderate diet modification while 325 patients were on moderate to severe diet modification. The study also noted that 232 males and 215 females took Complementary and Alternative Medicines (CAM). Of 447 patients, 12 showed menstrual abnormalities (2.6%), and 18 had mild diarrhoea (4%). The study also found that there is a vital significance of lowering FBS and HbA1c with the management strategies (p=0.000). The study showed a strong association between group 3 and improved FBS and HbA1c (p=0.000)., Conclusions: This study reveals that diet modification and regular exercise improve FBS and HbA1c levels significantly. Hence, diet modification and exercise can be added as adjuvants and should be incorporated into the management guidelines of T2DM.

Dapsone, which is used for treating dermatological conditions, can lead to neutropenia. Especially, resistant neutropenia makes patients vulnerable to invasive infections, indicating a medical emergency. Febrile neutropenia secondary to dapsone intake should be treated promptly before the development of sepsis, which may lead to shock and death. In addition, necrotizing fasciitis is a severe and potentially fatal soft-tissue infection that rarely develops in healthy individuals with skin lesions. In this report, we present a case of a patient with no comorbidities who presented with necrotizing fasciitis and neutropenia with a history of dapsone intake., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Abdur Raheem et al.)

Tyrosine kinases are known to play a role in tumour growth and proliferation, and they have become common drug targets. Tyrosine kinase inhibitors (TKIs) prohibit associated kinases from phosphorylating tyrosine residues in their substrates, preventing downstream signaling pathways from being activated. Multiple robust and well-tolerated TKIs targeting single or multiple targets, including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT, have been developed over the last two decades, contributing to our understanding of precision cancer medicine based on a patient's genetic alteration profile. The epidermal growth factor receptor (EGFR) family consists of four transmembrane tyrosine kinases (EGFR1/ErbB1, Her2/ErbB2, Her3/ErbB3, and Her4/ErbB4) and thirteen polypeptide ligands produced by them. Multiple solid tumours, including breast, pancreatic, head and neck, kidney, vaginal, renal, colon, and non-small cell lung cancer, overexpress EGFRs. Overexpression of these genes stimulates downstream signaling channels, causing cell proliferation, differentiation, cell cycle progression, angiogenesis, cell motility, and apoptosis inhibition. EGFRs' high expression and/or adaptive activation coincide with the pathogenesis and development of many tumours, making them appealing candidates for both diagnosis and therapy. Several strategies for targeting these receptors and/or the EGFR-mediated effects in cancer cells have been established. The majority of methods include the development of anti-EGFR antibodies and/or small-molecule EGFR inhibitors. This review presents the recent advances in EGFR TKIs and their role in the treatment of cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer has a significant social consequence all around the globe. In 2020, approximately 19.3 million new cases of cancer were diagnosed worldwide, with about 10 million cancer deaths. In the next two decades, suspected cases are anticipated to increase by roughly 47%. The rising number of cancer patients, as well as the inadequacy of traditional chemotherapeutic agents, radiation, and invasive surgical procedures, all rely on massive cell death with hardly any selectivity, causing severe toxicities. In comparison to synthetic medications, there has subsequently been a surge in international interest in non-synthetic and alternative remedies, owing to improved adaptability and reduced side effects of drug responses. Several people with cancer prefer alternative and complementary therapy treatments, and natural remedies play a crucial role in cancer chemoprevention as they are thought to be harmless, offer fewer negative effects, and become less sufficient to evoke addiction by the wider population. Chemopreventive, antimetastatic, cytotoxic, and anti-angiogenic actions are among the promising clinical advantages, which have been established in vitro research and certain clinical trials; nevertheless, additional clinical trials are needed. This review examines several phytochemicals that may have anti-cancer and chemopreventive properties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Glucokinase (GK) is an enzyme involved in synthesising glucose into glucose-6 phosphate and serves a crucial function in glucose sensing. Therefore, agents that induce GK activation could be used to treat T2DM. The present work has been carried out to investigate the GK activation potential of phytoconstituents of Enicostemma littorale through molecular docking. All the phytoconstituents have been screened through the Lipinski rule of 5, Veber's rule, and ADMET properties. From these initial screening, only Apigenin, Ferulic acid, Genkwanin, p-coumaric acid, Protocatechuic acid, Syringic acid, and Vanillic acid have been selected to perform molecular docking studies. The binding free energy and binding mode of the native ligand in the allosteric site of the enzyme have been considered the reference for the other molecules' validation. The native ligand has exhibited - 7.2 kcal/mol binding free energy, whereas; it has formed four hydrogen bonds with THR-228, LYS-169, ASP-78, and GLY-81. Based on these findings, the interactions of phytoconstituents have been justified. Apigenin, genkwanin, and swertiamarin exhibited - 8.7, - 7.5, and - 8.3 kcal/mol binding free energy, respectively, which indicates better enzyme activation than the native ligand. Swertiamarin has formed 08 hydrogen bonds with allosteric amino acid residues, which confirms the excellent enzyme activation by these phytoconstituents. We concluded that if we can isolate and consume the exact active phytoconstituents (GK activators) from this plant, we can use them effectively to treat T2DM. More GK activators can be developed by considering them as a natural lead moiety., Competing Interests: Conflict of interestDeclared none., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.)

Methacrylonitrile (MeAN) is a plastic monomer. Its effect on membrane bound enzymes like Na+K+ -ATPase, Ca2+ -ATPase, Mg2+ -ATPase, NADH dehydrogenase, alkaline phosphatase (ALP) and various elements like sodium (Na+), potassium (K+), and calcium (Ca2+) in rat brain were studied. Administration of 50 mg/kg body weight/day (0.25 LD50) and 100 mg/kg body weight/day (0.5 LD50) by gavage to rats for 7 days resulted in a significant decrease in activities of Na+K+ -ATPase, Ca2+ -ATPase, Mg2+ -ATPase, and NADH dehydrogenase. A significant reduction in calcium content, potassium content and a significant increase in sodium content and alkaline phosphatase activity in MeAN treated animals were observed. Inhibition of membrane bound enzymes occurred due to either direct effect of MeAN or indirect effect of changes in ionic homeostasis in MeAN treated animals.