Fabrication of an affordable and sensitive corticosteroid-binding globulin immunosensor based on electrodeposited gold nanoparticles modified glassy carbon electrode.

Herein, we fabricated an ultrasensitive electrochemical immunosensor for the quantitative detection of corticosteroid-binding globulin (CBG). CBG is a protein that regulates glucocorticoid levels and is an important biomarker for inflammation. A decrease in CBG levels is a key biomarker for inflammatory diseases, such as septic shock. To enhance the electrochemical performance and provide a large surface area for anti-CBG immobilization, we functionalized the glassy carbon electrode surface with AuNPs. Electrochemical characterization methods including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to examine the construction of the fabricated immunosensor. The electrochemical signal demonstrated a remarkable sensitivity to the CBG antigen, with a detection range from 0.01 to 100 µg/mL and a limit of detection of 0.012 µg/mL, making it suitable for both clinical and research applications. This label-free immunosensor offers significant advantages, including high sensitivity, low detection limits and excellent selectivity, making it a promising tool for detecting CBG in complex biological samples. Its potential applications include early disease diagnosis, treatment monitoring and studying CBG-related physiological processes.

Protective Effect of Hirsutidin against Rotenone-Induced Parkinsonism via Inhibition of Caspase-3/Interleukins-6 and 1ß.

A participant of the chemical family recognized as anthocyanins, hirsutidin is an O-methylated anthocyanidin. It is a natural substance, i.e., existing in Catharanthus roseus (Madagascar periwinkle), the predominant component in petals, as well as callus cultures. The literature review indicated a lack of scientifically verified findings on hirsutidin's biological activities, particularly its anti-Parkinson's capabilities. Using the information from the previous section as a reference, a present study has been assessed to evaluate the anti-Parkinson properties of hirsutidin against rotenone-activated Parkinson's in experimental animals. For 28 days, rats received hirsutidin at a dose of 10 mg/kg and rotenone at a dose of 0.5 mg/kg s.c. to test the neuroprotective effects. The hirsutidin was given 1 h before the rotenone. Behavioral tests, including the rotarod test, catalepsy, Kondziela's inverted screen activity, and open-field analysis, were performed. The levels of neurotransmitters (5-HT, DOPAC, 5-HIAA, dopamine, and HVA), neuroinflammatory markers (TNF-α, IL-6, IL-1ß, caspase-3), an endogenous antioxidant, nitrite content, and acetylcholine were measured in all the rats on the 29th day. Hirsutidin exhibited substantial behavioral improvement in the rotarod test, catalepsy, Kondziela's inverted screen activity, and open-field test. Furthermore, hirsutidin restored neuroinflammatory markers, cholinergic function, nitrite content, neurotransmitters, and endogenous antioxidant levels. According to the study, hirsutidin has anti-inflammatory and antioxidant characteristics. As a result, it implies that hirsutidin may have anti-Parkinsonian effects in rats.

Sterubin protects against chemically-induced Alzheimer's disease by reducing biomarkers of inflammation- IL-6/ IL-ß/ TNF-α and oxidative stress- SOD/MDA in rats.

Sterubin, a flavanone is an active chemical compound that possesses neuroprotective activity. The current investigation was intended to assess the sterubin effect in scopolamine-activated Alzheimer's disease. The rats were induced with scopolamine (1.5 mg/kg) followed by treatment with sterubin (10 mg/kg) for 14 days. Behavioural analysis was predictable by the Y-maze test and Morris water test. Biochemical variables like nitric oxide acetylcholinesterase, Choline acetyltransferase, antioxidant markers like superoxide dismutase, glutathione transferase, malondialdehyde, catalase, and myeloperoxidase activity, neuroinflammatory markers such as tumor necrosis factor-alpha, nuclear factor kappa B, interferon-gamma, interleukin (IL-1ß), and IL-6 were measured. The result stated that sterubin reversed the oxidative stress parameters, increased motor performance, and lowered the inflammatory markers in scopolamine-induced rats. The study demonstrated that sterubin possesses neuroprotective, anti-inflammatory, and antioxidant properties which can be used as a beneficial medication in AD.

Engineering processive cellulase of Clostridium thermocellum to divulge the role of the carbohydrate-binding module.

The processive cellulase (CelO) is an important modular enzyme of Clostridium thermocellum. To study the effect of the carbohydrate-binding module (CBM3b) on the catalytic domain of CelO (GH5), four engineered derivatives of CelO were designed by truncation and terminal fusion of CBM3b. These are CBM at the N-terminus, native form (CelO-BC, 62 kDa); catalytic domain only (CelO-C, 42 kDa); CBM at the C-terminus (CelO-CB, 54 kDa) and CBM attached at both termini (CelO-BCB, 73 kDa). All constructs were cloned into pET22b (+) and expressed in Escherichia coli BL21 (DE3) star. The expression levels of CelO-C, CelO-CB, CelO-BC, and CelO-BCB were 35%, 35%, 30%, and 20%, respectively. The enzyme activities of CelO-C, CelO-CB, CelO-BC, and CelO-BCB against 1% regenerated amorphous cellulose (RAC) were 860, 758, 985, and 1208 units per µmole of the enzyme, respectively. The enzymes were partially purified from the lysate of E. coli cells by heat treatment followed by anion exchange FPLC purification. Against RAC, CelO-C, CelO-CB, CelO-BC, and CelO-BCB showed KM values of 32, 33, 45, and 43 mg⋅mL-1 and Vmax values of 3571, 3846, 3571, and 4545 U⋅min-1 , respectively. CBM3b at the N-terminus of GH5 linked through a P/T-rich linker was found to enhance the catalytic activity and thermostability of the enzyme.

Environment friendly green synthesis method based natural bioactive functional "catechin and gingerol" loaded nanomedicine for the management of obesity.

Obesity is one of the major health problems across the world and the leading cause of death. Natural bioactive functional compounds (catechin, Cat and gingerol, Gin) have been reported to control obesity. The application of a nanoparticulate (NPs) delivery system has shown greater efficacy in the treatment of different diseases. The present study was designed to prepare the Cat-Gin silver nanoparticles (AgNPs) using the microwave method. The prepared Cat-Gin-AgNPs were characterized for particle size, zeta potential, encapsulation efficiency and drug release. Further, it was evaluated for anti-obesity activity (body weight, total abdominal fat, lipid profile and liver profile) using a high-fed diet (HFD) induced obesity model. The formulated Cat-Gin-AGNPs showed nano-metric size (110 ± 4.65 nm), polydispersity index (PDI) of 0.27 ± 0.03, and surface charge (-17.6 ± 2.6 mV) with a spherical shape. It also depicted high encapsulation efficiency (<80 %) with prolonged drug release behaviour (Cat - 84.34 ± 4.12 % and Gin - 72.33 ± 3.87 %). The in vivo study parameters revealed a significant (p ≤ 0.001) reduction in body weight, food intake and total abdominal fat. The biochemical results displayed a reversal in altered biochemical parameters to the normal range (Group 4) as compared to HFD control (Group 2). It also helps restored the liver enzymes in obese rats. The results of the study highlighted the applicability of Cat-Gin-AGNPs as a novel delivery system in the treatment of obesity.

Effects of the Anthocyanin Hirsutidin on Gastric Ulcers: Improved Healing through Antioxidant Mechanisms.

The goal of this study was to determine the effect of hirsutidin on ethanol-induced stomach ulcers in rats. Rats (n = 24 rats/group) were separated at random into the following groups: normal saline-treated (normal control), ethanol-treated (ethanol control), 10 mg/kg hirsutidin + ethanol-treated (hirsutidin 10), and 20 mg/kg hirsutidin + ethanol-treated (hirsutidin 20). All the groups received the respective treatment orally for 7 days. On day 7, i.e., after 24 h of fasting, except for the normal control group, all the groups orally received 5 mL/kg of ethanol. Four hours later, rats were anaesthetized, serum was isolated from the blood, and biochemical tests were performed. The stomach tissue was utilized for ulcer grading, histology, and biochemical analysis. The rats developed stomach acidity and ulcers after being given ethanol based on increased ulcer score, disturbed cellular architecture, increased oxidative stress, myeloperoxidase and decreased endogenous antioxidants, and nitric oxide and prostaglandin E2 concentration. Ethanol-treated rats also displayed increased tumor necrosis factor-α, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and inflammatory cytokines. The treatment with hirsutidin protected and significantly restored all serum parameters in ethanol-induced stomach ulcers and may have antiulcer activity.

Antiamnesic Potential of Malvidin on Aluminum Chloride Activated by the Free Radical Scavenging Property.

Objectives: Malvidin, a dietary anthocyanin can be a potent drug for the treatment of neuronal toxicity. The investigation was aimed to study the antioxidant role of malvidin against aluminum chloride (AlCl3)-induced neurotoxicity in rats. Methods: To evaluate the neuroprotective role of malvidin, the rats were divided into four different groups: group I received saline, group II received AlCl3, and groups III and IV were administered with 100 and 200 mg/kg malvidin after AlCl3 for 60 days. During the evaluation period, all the groups were subjected to a behavioral test. On the 61st day of the study, rat brains were removed and used for a neurochemical assay. Results: From the present study, malvidin ameliorated the effects of AlCl3 on behavioral parameters. Biochemical investigation revealed that oral treatment of malvidin shows neuroprotective effects through regulation of antioxidant levels and neuroinflammation in the AlCl3-exposed rats. Conclusion: The results indicate that malvidin possesses antioxidant activity via acetylcholinesterase inhibition and regulation of oxidative stress in neuronal cells. Hence, malvidin could be a potential drug in correcting Alzheimer's disease.

Design, Synthesis, and Bioevaluation of Indole Core Containing 2-Arylidine Derivatives of Thiazolopyrimidine as Multitarget Inhibitors of Cholinesterases and Monoamine Oxidase A/B for the Treatment of Alzheimer Disease.

In continuation of our previous study to identify multitarget inhibitors of cholinesterases (ChEs) and monoamine oxidase (MAOs) isoforms, we synthesized and evaluated 2-arylidine derivatives of thiazolopyrimidine for the treatment of Alzheimer disease. Three series of compounds with different linker size and target-anchoring functional groups were synthesized. Compounds 34-37 showed excellent to good AChE and BChE inhibition potential at nanomolar to low micromolar concentration. While all the compounds showed excellent MAO-B inhibition and selectivity relative to MAO-A, compounds 25 and 36 emerged as the most potent MAO-B inhibitors of all the series of synthesized compounds with IC50 values of 0.13 µM and 0.10 µM, respectively. Furthermore, kinetic studies of inhibitor 35 showed mixed inhibition mode. Exploration of structure activity relationship (SAR) revealed the role of functionalities and length of linkers on potency. Acute toxicity evaluation showed the safety of tested compounds up to 2000 mg/kg dose. PAMPA-BBB evaluation showed BBB permeability of the tested compounds, while MTT assay performed on neuroblastoma SHSY5Y cells showed that all the tested compounds are non-neurotoxic in the tested concentrations. Docking studies showed a strong correlation with experimental in vitro results via binding orientations and interaction patterns of the synthesized compounds into the binding sites of target enzymes. We have successfully identified safe, non-neurotoxic, and blood brain barrier permeable multitarget lead compounds for the treatment of AD.

Fustin ameliorates hyperglycemia in streptozotocin induced type-2 diabetes via modulating glutathione/Superoxide dismutase/Catalase expressions, suppress lipid peroxidation and regulates histopathological changes.

Streptozotocin (STZ) 60 mg/kg, i.p.-induced diabetes in rat's results into hyperglycemia, impaired oxidative stress, lipid profile, insulin levels and changes in body weight. Treatment with antihyperglycemics and antioxidants are accounted to produce favorable effect in this paradigm. Fustin, a flavonoid derived from Rhus verniciflua, extract of Rhus verniciflua reported to exhibit anti-hyperglycemic, antioxidant, anti-microbial, anti-arthritic effects, anti-obesity effects, antiplatelet effects and anti-cancer effects. However, no evidence is existing on effect of fustin on STZ-induction diabetes. Thus, we evaluated its effects against diabetes in STZ-induced rodents. Blood glucose, Insulin, lipid peroxidation (MDA), superoxide dismutase (SOD), catalase activity (CAT), glutathione (GSH) and lipid profile levels was assessed. After 30 days diabetes induction rodents showed a severe increased blood sugar level, MDA, high density lipid and decreased cholestrol, triglyceride, GSH, SOD, CAT, respectively. Oppositely, treatment with fustin (50-100 mg/kg/p.o., two times daily, 30 days) enhanced blood glucose, lipid profile levels Insulin. Meanwhile, reduced MDA and enhanced GSH, SOD, and CAT in diabetic rats. Glibenclamide 5 mg/kg/p.o. also enhanced diabetes-induced complications and decreased oxidative stress. Further histopathology of pancreas confirms the protective effect fustin in STZ-induction diabetes in animals. In conclusion, the study revealed treatments with fustin avoid the changes in body weight, blood glucose, lipid profile and oxidative stress. As a results of these finding may lead to the growth of a choice of medicine for hyperglycemic in the future.

COVID-19: Prospective Challenges and Potential Vaccines.

CONTEXT: RNA viruses exhibit an extraordinary ability to evolve in a changing environment and to switch from animal hosts to humans. The ongoing COVID-19 pandemic, recognized as a respiratory disease, is an example of zoonotic transmission of the RNA virus known as SARS-CoV-2. The development and regulatory approval of a vaccine against SARS-CoV-2 pose multiple preventive and therapeutic challenges, especially during an ongoing pandemic. OBJECTIVE: The review intended to examine the challenges and recent achievements in the development of vaccine candidates against COVID-19. DESIGN: The research team performed a literature review, searching relevant and up to date information from the literature. The sources of data included Google Scholar, PubMed, NCBI, and Yahoo. The search terms used were COVID-19 challenges, SARS-CoV-2 prospective challenges, RNA viruses adoptability, host switching by RNA viruses, COVID-19 vaccines. SETTING: The study took place at the digital libraries of contributing institutions. The data was combined, selected for further analysis and manuscript preparation at King Abdulaziz University. RESULTS: RNA viruses with high rate of genome alterations and evolution have better chances to survive in the adverse environmental conditions by adopting the alternate host species. The recent epidemics such as SARS, MERS, and COVID-19 are examples of zoonotic transmission of RNA viruses from animal species to the humans. However, the mechanisms involved in the switching-on to new host species need further investigations to control the zoonotic transmissions in near future. As of April 2020, 115 candidate vaccines were being evaluated; 78 of them had been found to be active, and a few of them are in Phase I trials. In the development of different types of vaccine candidates against COVID-19, multiple international pharmaceutical and biotechnology companies are involved. CONCLUSIONS: Emerging and re-emerging pathogenic RNA viruses pose a serious threat to human health. Little is known about the human-host adoptive mechanism for zoonotic transmission. Deep insights into the molecular mechanism responsible for the switching of animal or bird viruses to humans could provide target molecules or events to prevent such transmissions in the near future. Fast development and approval of efficacious and safe vaccines is key to the effort to provide preventive measures against COVID-19 and future viruses. However, the development and availability of a vaccine candidate is a time-consuming process and often can't be completed during an epidemic. Currently, several types of vaccines are under development, and most of them won't realistically be available in time for the present COVID-19 pandemic.

High Y-chromosomal Differentiation Among Ethnic Groups of Dir and Swat Districts, Pakistan.

The ethnic groups that inhabit the mountainous Dir and Swat districts of northern Pakistan are marked by high levels of cultural and phenotypic diversity. To obtain knowledge of the extent of genetic diversity in this region, we investigated Y-chromosomal diversity in five population samples representing the three main ethnic groups residing within these districts, including Gujars, Pashtuns and Kohistanis. A total of 27 Y-chromosomal short tandem repeats (Y-STRs) and 331 Y-chromosomal single nucleotide polymorphisms (Y-SNPs) were investigated. In the Y-STRs, we observed very high and significant levels of genetic differentiation in nine of the 10 pairwise between-group comparisons (RST 0.179-0.746), and the differences were mirrored in the Y-SNP haplogroup frequency distribution. No genetic differences were found between the two Pashtun subethnic groups Tarklanis and Yusafzais (RST = 0.000). Utmankhels, also considered Pashtuns culturally, were not closely related to any of the other population samples (RST 0.451-0.746). Thus, our findings provide examples of both associations and dissociations between cultural and genetic legacies. When analyzed within a larger continental-scale context, these five ethnic groups fall mostly outside the previously characterized Y-chromosomal gene pools of the Indo-Pakistani subcontinent. Male founder effects, coupled with culturally and topographically based constraints upon marriage and movement, are likely responsible for the high degree of genetic structure in this region.