Facile synthesis of elastin nanogels encapsulated decursin for castrated resistance prostate cancer therapy.

Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/ßcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.

Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome.

Introduction: Polycystic Ovary syndrome (PCOS) affects the health of many women around theworld. Apart from fundamental metabolic problems connected to PCOS, focus of our study is on the role of quercetin on genes relevant to steroidogenesis and folliculogenesis. Methods: Eighteen mature parkes strain mice (4-5 weeks old) weighing18-21 g were randomly divided into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kgbw) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days. Results: In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH ratio, decreased estrogen level and decline in expression of Kitl, Bmp1, Cyp11a1, Cyp19a1, Ar, lhr, Fshr and Esr1 in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in cholesterol, triglycerides, testosterone, vascular endothelial growth factor VEGF and insulin levels. All these changes were reversed after the administration of quercetin in PCOS mice. Discussion: Quercetin treatment reversed the molecular, functional and morphological abnormalities brought on due to letrozole in pathological and physiological setting, particularly the issues of reproduction connected to PCOS. Quercetin doesn't act locally only but it acts systematically as it works on Pituitary (LH/FSH)- Ovary (gonad hormones) axis. the Side effects of Quercetin have to be targeted in future researches. Quercetin may act as a promising candidate for medical management of human PCOS.

Neem (Azadirachta Indica) and silk fibroin associated hydrogel: Boon for wound healing treatment regimen.

Background & Objectives: Wound healing is the complex physiological process of replacing damaged cells or tissue layers. The neem (Azadirachta Indica) has a variety of biological activities, which may hasten the rate at which the wound healing mechanism occurs. Silk fibroin is a biomaterial that is reported for its tissue regeneration activity. So, the present study was designed to assess the effectiveness of a hydrogel comprising neem and silk fibroin biomaterials for the treatment of wounds. Methods: Topical neem hydrogels (N-HG) with and without silk fibroin (N-SFB-HG) were prepared using neem extract, silk fibroin, and guar gum, which act by entrapping the components by forming a gel. Evaluation tests such as Fourier transform infrared spectroscopy (FT-IR), visual emergence, pH, rheological behavior, spreading capacity, drug content, skin irritation, anti-microbial action, in vivo wound healing activity, and stability were carried out. Results: The FT-IR results showed no chemical interaction between the constituents. The formed hydrogels had pH values of 5.87 ± 0.3 for N-HG and 5.76 ± 0.2 for N-SFB-HG. The preferred topical gel viscosity was observed in the N-HG (54.2 ± 3.2cPs) and N-SFB-HG (59.9 ± 4.8cPs) formulations. The formulated hydrogels were sterile and did not irritate the skin. The in vivo wound healing investigation results reveal that the N-SF-HG treatment speeds up the regeneration of the injured area faster when compared to control and N-HG treated groups. Interpretation & Conclusion: These results support the efficacy of the topical hydrogel formulation, including neem and silk fibroin. Therefore, the neem-silk fibroin hydrogel formulation is a therapeutically viable choice that, following necessary clinical research, might be utilized in novel formulations for managing chronic wounds.

Addressing the resurgence of global monkeypox (Mpox) through advanced drug delivery platforms.

Monkeypox (Mpox) is a transmissible infection induced by the Monkeypox virus (a double-stranded DNA virus), recognised under the family orthopoxvirus genus. Monkeypox, like endemic diseases, is a substantial concern worldwide; thus, comprehending the pathogenesis and mutagenesis of amino acids is indispensable to combat the infection. According to the World Health Organization's report, about 89 thousand cases with 160 mortalities have been reported from 114 countries worldwide. The conventional orthopoxvirus vaccines developed on live attenuated viruses exempted any clinical validation from combating monkeypox due to inadequate immunogenicity, toxicity, instability, and multiple doses. Therefore, novel drug delivery systems come into the conception with high biological and mechanical characteristics to address the resurgence of Global Monkeypox. The edges of metallic biomaterials, novel molecules, and vaccine development in targeted therapy increase the modulation of the immune response and blockage of host-virus interaction, with enhanced stability for the antigens. Thus, this review strives to comprehend the viral cell pathogenesis concerning amino acid mutagenesis and current epidemiological standards of the Monkeypox disease across the globe. Furthermore, the review also recapitulates the various clinical challenges, current therapies, and progressive nanomedicine utilisation in the Monkeypox outbreak reinforced by various clinical trial reports. The contemporary challenges of novel drug delivery systems in Monkeypox treatment cannot be overlooked, and thus, authors have outlined the future strategies to develop successful nanomedicine to combat monkeypox. Future pandemics are inevitable but can be satisfactorily handled if we comprehend the crises, innovate, and develop cutting-edge technologies, especially by delving into frontiers like nanotechnology.

Potential benefits of using chitosan and silk fibroin topical hydrogel for managing wound healing and coagulation.

Background & Objectives: The intricate process of wound healing involves replacing the cellular or tissue structure that has been destroyed. In recent years various wound dressings were launched but reported several limitations. The topical gel preparations are intended for certain skin wound conditions for local action. Chitosan-based hemostatic materials are the most effective in halting acute hemorrhage, and naturally occurring silk fibroin is widely utilized for tissue regeneration. So, this study was conducted to evaluate the potential of chitosan hydrogel(CHI-HYD) and chitosan silk fibroin hydrogel (CHI-SF-HYD) on blood clotting and wound healing. Methods: Hydrogel was prepared using various concentrations of silk fibroin with guar gum as a gelling agent. The optimized formulations were evaluated for visual appearance, Fourier transforms infrared spectroscopy (FT-IR), pH, spreadability, viscosity, antimicrobial activity, HR-TEM analysis, ex vivo skin permeation, skin irritation, stability studies, and in vivo studies by using adult male Wistar albino rats. Results: Based on the outcome of FT-IR, no chemical interaction between the components was noticed. The developed hydrogels exhibited a viscosity of 79.2 ± 4.2 Pa.s (CHI-HYD), 79.8 ± 3.8 Pa.s (CHI-SF-HYD), and pH of 5.87 ± 0.2 (CHI-HYD), 5.96 ± 0.1 (CHI-SF-HYD). The prepared hydrogels were sterile and non-irritant to the skin. The in vivo study outcomes show that the CHI-SF-HYD treated group has significantly shortened the span of tissue reformation than other groups. This demonstrated that the CHI-SF-HYD could consequently accelerate the regeneration of the damaged area. Interpretation & Conclusion: Overall, the positive outcomes revealed improved blood coagulation and re-epithelialization. This indicates that the CHI-SF-HYD could be used to develop novel wound-healing devices.

Nipah and Hendra Viruses: Deadly Zoonotic Paramyxoviruses with the Potential to Cause the Next Pandemic.

Nipah and Hendra viruses are deadly zoonotic paramyxoviruses with a case fatality rate of upto 75%. The viruses belong to the genus henipavirus in the family Paramyxoviridae, a family of negative-sense single-stranded RNA viruses. The natural reservoirs of NiV and HeV are bats (flying foxes) in which the virus infection is asymptomatic. The intermediate hosts for NiV and HeV are swine and equine, respectively. In humans, NiV infections result in severe and often fatal respiratory and neurological manifestations. The Nipah virus was first identified in Malaysia and Singapore following an outbreak of encephalitis in pig farmers and subsequent outbreaks have been reported in Bangladesh and India almost every year. Due to its extreme pathogenicity, pandemic potential, and lack of established antiviral therapeutics and vaccines, research on henipaviruses is highly warranted so as to develop antivirals or vaccines that could aid in the prevention and control of future outbreaks.

Mucormycosis an added burden to Covid-19 Patients: An in-depth systematic review.

As of 25th July, 2022, global Disease burden of 575,430,244 confirmed cases and over 6,403,511 deaths have been attributed to coronavirus disease 2019 (COVID-19). Co-infections/secondary infections continue to plague patients around the world as result of the co-morbidities like diabetes mellitus, biochemical changes caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) especially significant elevation in free iron levels, immune suppression caused by SARS-CoV-2, and indiscriminate use of systemic corticosteroids for the treatment of severe COVID-19 disease. In such circumstances, opportunistic fungal infections pose significant challenge for COVID-19 disease therapy in patients with other co-morbidities. Although COVID-19-associated Mucormycosis (CAM) has been widely recognized, currently extensive research is being conducted on mucormycosis. It has been widely agreed that patients undergoing corticosteroid therapy are highly susceptible for CAM, henceforth high index of screening and intensive care and management is need of an hour in order to have favorable outcomes in these patients. Diagnosis in such cases is often delayed and eventually the disease progresses quickly which poses added burden to clinician and increases patient load in critical care units of hospitals. A vast perusal of literature indicated that patients with diabetes mellitus and those with other co-morbidities might be highly vulnerable to develop mucormycosis. In the present work, the case series of three patients presented at Chest Disease Hospital Srinagar, Jammu and Kashmir infected with CAM has been described with their epidemiological data in supplementary section. All these cases were found to be affected with co-morbidity of Diabetes Mellitus (DM) and were under corticosteroid therapy. Furthermore, given the significant death rate linked with mucormycosis and the growing understanding of the diseases significance, systematic review of the literature on CAM has been discussed and we have attempted to discuss emerging CAM and related aspects of the disease.

LRFN2 gene variant rs2494938 provides susceptibility to esophageal cancer in the population of Jammu and Kashmir.

BACKGROUND: Leucine-rich repeat and fibronectin type 2 gene (LRFN2) variant rs2494938 has recently been found associated with esophageal cancer in a genome-wide association study in an Asian population. However, this association has not been replicated in any Indian population despite high incidence of the disease. MATERIALS AND METHODS: In the present case-control study, 166 cases and 459 controls were included. Taqman assay technique using real-time PCR was employed to investigate the association of the variant with esophageal cancer in the population of Jammu and Kashmir (J&K). The Hardy-Weinberg equilibrium for rs2494938 was assessed using the Chi-square test. The allele- and genotype-specific risk was estimated by odds ratio (OR) with 95% confidence interval (CI). RESULTS: Variant rs2494938 was observed to be significantly associated with esophageal cancer with an allelic OR of 1.59 (1.23-2.04 at 95% CI, P = 0.0003). CONCLUSION: The study highlights LRFN2 as a candidate gene for esophageal cancer susceptibility in the population of J&K and calls for a detailed study with a large sample size and involving more ethnic groups of India.

Novel Ergot Alkaloids Production from Penicillium citrinum Employing Response Surface Methodology Technique.

Ergot alkaloids are novel pharmaceutical and therapeutic agents synthesized in this study using fungal species Penicillium citrinum. To get the maximum yield of ergot alkaloids a statistical process of response surface methodology was employed using surface culture fermentation technique. Initially, the strain of Penicillium was improved using physical (ultraviolet (UV) and chemical (ethyl methane sulfonate (EMS) treatments to get the maximum yield of ergot alkaloids through surface culture fermentation technique. After improving the strain, survival rate of colonies of Penicillium citrinum treated with UV and EMS was observed. Only 2.04% living colonies were observed after 150 min of exposure of Penicillium citrinum in UV light and 3.2% living colonies were observed after 20 min of the exposure in EMS. The mutated strains of Penicillium citrinum were screened for their production of ergot alkaloids and after fermentation experiments, maximum yield was obtained from PCUV-4 and PCEMS-1 strains. After strain improvement, Plackett-Burman design (PBD) and Box-Behnken design (BBD) of RSM were employed and 10-fold yield enhancement (35.60 mg/100 mL) of ergot alkaloids was achieved. This enhancement in yield of ergot alkaloids proved the positive impacts of RSM and UV on the yield of ergot alkaloids. The study provides a cost effective, economical and sustainable process to produce medically important ergot alkaloids which can be used in various pharmaceutical formulations to treat human diseases.

Assessment of biochemical and antioxidative status in patients suffering from dengue fever.

A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.

Assessment of biochemical and antioxidative status in patients suffering from dengue fever / 华中科技大学学报（医学）（英德文版）

A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.

Assessment of biochemical and antioxidative status in patients suffering from dengue fever / 华中科技大学学报（医学）（英德文版）

A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.

Hepatoprotective Effects of Silybum marianum (Silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in Combination: A Possible Synergy.

Oxidative stress, lipid peroxidation, and transaminase reactions are some of the mechanisms that can lead to liver dysfunction. A time-dependent study was designed to evaluate the ability of silymarin (SLN) and glycyrrhizin (GLN) in different dosage regimens to lessen oxidative stress in the rats with hepatic injury caused by the hepatotoxin carbon tetrachloride. Wistar male albino rats (n = 60) were randomly assigned to six groups. Group A served as a positive control while groups B, C, D, E, and F received a dose of CCl4 (50% solution of CCl4 in liquid paraffin, 2 mL/kg, intraperitoneally) twice a week to induce hepatic injury. Additionally, the animals received SLN and GLN in different doses for a period of six weeks. CCl4 was found to induce hepatic injury by significantly increasing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and thiobarbituric acid reactive substances while decreasing total protein and the activities of reduced glutathione, superoxide dismutase, and catalase. Treatment with various doses of SLN and GLN significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Our findings indicated that SLN and GLN have hepatoprotective effects against oxidative stress of the liver.