Binding selectivity analysis of new delhi metallo-beta-lactamase-1 inhibitors using molecular dynamics simulations: Exploring possibilities for decoding antimicrobial drug resistance.

BACKGROUND: New Delhi metallo-beta-lactamase-1 (NDM1) confers resistance to several bacterial species against a broad range of beta-lactam antibiotics and turning them into superbugs that pose a significant threat to healthcare systems worldwide. As such, it is a potentially relevant biological target for counteracting bacterial infections. Given the lack of effective treatment options against NDM1 producing bacteria, finding a reliable inhibitor for the NDM1 enzyme is crucial. METHODS: Using molecular dynamics simulations, the binding selectivities and affinities of three ligands, viz. PNK, 3S0, and N1G were investigated against NDM1. RESULTS: The results indicate that N1G binds with more affinity to NDM1 than PNK and 3S0. The binding energy decomposition analysis revealed that residues I35, W93, H189, K211, and N220 showed significant binding energies with PNK, 3S0, and N1G, and hence are crucially involved in the binding of the ligands to NDM1. Molecular dynamics trajectory analysis further elicited that the ligands influence dynamic flexibility of NDM1 morphology, which contributes to the partial selectivities of PNK, 3S0, and N1G. CONCLUSIONS: This in silico study offers a vital information for developing potential NDM1 inhibitors with high selectivity. Nevertheless, in vitro and in vivo experimental validation is mandated to extend the possible applications of these ligands as NDM1 inhibitors that succor in combating antimicrobial resistance.

Ganoderma lucidum: Multifaceted mechanisms to combat diabetes through polysaccharides and triterpenoids: A comprehensive review.

Diabetes is a chronic metabolic disorder. Diabetes complications can affect many organs and systems in the body. Ganoderma lucidum (G. lucidum) contains various compounds that have been studied for their potential antidiabetic effects, including polysaccharides, triterpenoids (ganoderic acids, ganoderol B), proteoglycans, and G. lucidum extracts. G. lucidum polysaccharides (GLPs) and triterpenoids have been shown to act through distinct mechanisms, such as improving glucose metabolism, modulating the mitogen-activated protein kinase (MAPK) system, inhibiting the nuclear factor-kappa B (NF-κB) pathway, and protecting the pancreatic beta cells. While GLPs exhibit a significant role in controlling diabetic nephropathy and other associated complications. This review states the G. lucidum antidiabetic mechanisms of action and potential biologically active compounds that contribute to diabetes management and associated complications. To make G. lucidum an appropriate replacement for the treatment of diabetes with fewer side effects, more study is required to completely comprehend the number of physiologically active compounds present in it as well as the underlying cellular mechanisms that influence their effects on diabetes.

Targeting tumour markers in ovarian cancer treatment.

Ovarian cancers (OC) are the most common, lethal, and stage-dependent cancers at the global level, specifically in female patients. Targeted therapies involve the administration of drugs that specifically target the alterations in tumour cells responsible for their growth, proliferation, and metastasis, with the aim of treating particular patients. Presently, within the realm of gynaecological malignancies, specifically in breast and OCs, there exist various prospective therapeutic targets encompassing tumour-intrinsic signalling pathways, angiogenesis, homologous-recombination deficit, hormone receptors, and immunologic components. Breast cancers are often detected in advanced stages, primarily due to the lack of a reliable screening method. However, various tumour markers have been extensively researched and employed to evaluate the condition, progression, and effectiveness of medication treatments for this ailment. The emergence of recent technological advancements in the domains of bioinformatics, genomics, proteomics, and metabolomics has facilitated the exploration and identification of hitherto unknown biomarkers. The primary objective of this comprehensive review is to meticulously investigate and analyze both established and emerging methodologies employed in the identification of tumour markers associated with OC.

Medicinal and chemosensing applications of chitosan based material: A review.

Chitosan (CTS), has emerged as a highly intriguing biopolymer with widespread applications, drawing significant attention in various fields ranging from medicinal to chemosensing. Key characteristics of chitosan include solubility, biocompatibility, biodegradability and reactivity, making it versatile in numerous sectors. Several derivatives have been documented for their diverse therapeutic properties, such as antibacterial, antifungal, anti-diabetic, anti-inflammatory, anticancer and antioxidant activities. Furthermore, these compounds serve as highly sensitive and selective chemosensor for the detection of various analytes such as heavy metal ions, anions and various other species in agricultural, environmental and biological matrixes. CTS derivatives interacting with these species and give analytical signals. In this review, we embark on an exploration of the latest advancements in CTS-based materials, emphasizing their noteworthy contributions to medicinal chemistry spanning the years from 2021 to 2023. The intrinsic biological and physiological properties of CTS make it an ideal platform for designing materials that interact seamlessly with biological systems. The review also explores the utilization of chitosan-based materials for the development of colorimetric and fluorimetric chemosensors capable of detecting metal ions, anions and various other species, contributing to advancements in environmental monitoring, healthcare diagnostics, and industrial processes.

Revolutionizing and identifying novel drug targets in Citrobacter koseri via subtractive proteomics and development of a multi-epitope vaccine using reverse vaccinology and immuno-informatics.

Citrobacter koseri is a gram-negative rod that has been linked to infections in people with significant comorbidities and immunocompromised immune systems. It is most commonly known to cause urinary tract infections. Thus, the development of an efficacious C. koseri vaccine is imperative, as the pathogen has acquired resistance to current antibiotics. Subtractive proteomics was employed during this research to identify potential antigenic proteins to design an effective vaccine against C. koseri. The pipeline identified two antigenic proteins as potential vaccine targets: DP-3-O-acyl-N-acetylglucosamine deacetylase and Arabinose 5-phosphate isomerase. B and T cell epitopes from the specific proteins were forecasted employing several immunoinformatic and bioinformatics resources. A vaccine was created using a combination of seven cytotoxic T cell lymphocytes (CTL), five helper T cell lymphocyte (HTL), and seven linear B cell lymphocyte (LBL) epitopes. An adjuvant (ß-defensin) was added to the vaccine to enhance immunological responses. The created vaccine was stable for use in humans, highly antigenic, and non-allergenic. The vaccine's molecular and interactions binding affinity with the human immunological receptor TLR3 were studied using MMGBSA, molecular dynamics (MD) simulations, and molecular docking analyses. E. coli (strain-K12) plasmid vector pET-28a (+) was used to examine the ability of the vaccine to be expressed. The vaccine shows great promise in terms of developing protective immunity against diseases, based on the results of these computer experiments. However, in vitro and animal research are required to validate our findings.Communicated by Ramaswamy H. Sarma.

Green synthesis of MgO nanoparticles and its antibacterial properties.

Magnesium oxide nanostructured particles (NP) were prepared using a simple solution combustion technique using different leaf extracts such as Mangifera indica (Mango - Ma), Azadirachta indica (Neem-Ne), and Carica papaya (Papaya-Pa) as surfactants. The highly crystalline phase of MgO nanostructures was confirmed by PXRD and FTIR studies for 2 h 500°C calcined samples. To analyze the characteristics of obtained material-MaNP, NeNP, and PaNP for dosimetry applications, thermoluminescence (TL) studies were carried out for Co-60 gamma rays irradiated samples in the dose range 10-50 KGy; PaNP and NeNP exhibited well-defined glow curve when compared with MaNP samples. In addition, it was observed that the TL intensity decreases, with increase in gamma dose and the glow peak temperature is shifted towards the higher temperature with the increase in heating rate. The glow peak was segregated using glow curve deconvolution and thermal cleaning method. Kinetic parameters estimated using Chen's method, trap depth (E), and frequency factor (s) were found to be 0.699, 7.408, 0.4929, and 38.71, 11.008, and 10.71 for PaNP, NeNP, and MaNP respectively. The well-resolved glow curve, good linear behavior in the dose range of 10-50, KGy, and less fading were observed in PaNP as compared with MaNP and NeNP. Further, the antibacterial activity was checked against human pathogens such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. A visible zone of clearance was observed at 200 and 100 µg/mL by the PaNP and NeNP, indicating the death of colonies by the nanoparticles. Therefore, PaNP nanomaterial is a potential phosphor material for dosimetry and antibacterial application compared to NeNP and MaNP.

Thymoquinone, piperine, and sorafenib combinations attenuate liver and breast cancers progression: epigenetic and molecular docking approaches.

BACKGROUND: Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells. METHODS: We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3. RESULTS: Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death. CONCLUSION: This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.

Heterocyclic Organic Compounds as a Fluorescent Chemosensor for Cell Imaging Applications: A Review.

Fluorometric determination of different biologically, industrially, and environmentally important analytes is a powerful technique because this technique has excellent selectivity, high sensitivity, rapid photoluminescence response, low cost, applicability to bioimaging, and low detection limit. Fluorescence imaging is a powerful technique for screening different analytes in the living system. Heterocyclic organic compounds have been extensively used as a fluorescence chemosensor for the determination of different biologically important cations like Co2+, Zn2+, Cu2+, Hg2+, Ag+, Ni2+, Cr3+, Al3+, Pd2+, Fe3+ Pt2+, Mn2+, Sn2+, Pd2+, Au3+, Pd2+, Cd2+, Pb2+ and other ions in biological and environmental systems. These compounds also showed significant biological applications such as anti-cancer, anti-ulcerogenic, antifungal, anti-inflammatory, anti neuropathic, antihistaminic, antihypertensive, analgesic, antitubercular, antioxidant, antimalarial, antiparasitic, antiglycation, antiviral anti-obesity, and antibacterial potency. In this review, we summarize the heterocyclic organic compounds based on fluorescent chemosensors and their applications in bioimaging studies for the recognition of different biologically important metal ions.

The growth hormone gene polymorphism and its relationship to performance and carcass features in Egyptian Awassi lambs.

The main purpose of the existing experiment was to assess the allelic and genotypic polymorphisms of the Growth hormone (GH) gene and its correlation with growth indices, efficiency of consumed feed, some body indices and carcass traits of the Egyptian Awassi sheep. Forty Egyptian Awassi male lambs were selected for their growing indices (post-weaning daily gain, marketing weight, and weaning weight), feed efficiency (consumed feed and of consumed feed), body conformational indicators (skeletal muscle index, relative body index, body mass index, and body index), and carcass features (dressing %, hot carcass weight, fore-legs %, neck %, loin %, ribs %, abdominal fat %, Tail % and hind-legs %). The polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) tool was applied to detect the genotypic and allelic GH gene polymorphisms properties. The PCR-RFLP analysis identified three main genotypes (AA, AB and BB) and two main alleles (A and B). The GH genotype (AA or AB) exhibited moderate significant influence (P < 0.05) on marketing weight, Loin% and Tail%. Also, genotype (AB or BB) of expressed GH gene significantly (P < 0.01) influence on consumed feed, post-weaning daily gain, neck% and body mass index, whereas, it had no influence on the phenotypic values of the other characteristics investigated. The presence of the A allele in the genotype was markedly associated (P < 0.01) with consumed feed, body mass index and post-weaning daily growth; conversely, the presence of the B allele in the genotype was significantly related (P < 0.05) with marketing weight, loin %, and tail %. While, GH gene expression was revealed to be highly significant (P < 0.01) in relation to post-weaning daily growth, feed intake, and neck %. According to the findings, determining the associations between GH gene variation and growth, efficiency of consumed feed, body measurements, and carcass features of Egyptian Awassi sheep and applying marker assisted selection with the GH gene to improve these traits is warranted and will be of significant economic value to sheep production.

Guaiazulene and related compounds: A review of current perspective on biomedical applications.

BACKGROUND: Thousands of people worldwide pass away yearly due to neurological disorders, cardiovascular illnesses, cancer, metabolic disorders, and microbial infections. Additionally, a sizable population has also been impacted by hepatotoxicity, ulcers, gastroesophageal reflux disease, and breast fissure. These ailments are likewise steadily increasing along with the increase in life expectancy. Finding innovative therapies to cure and consequently lessen the impact of these ailments is, therefore, a global concern. METHODS AND MATERIALS: All provided literature on Guaiazulene (GA) and its related compounds were searched using various electronic databases such as PubMed, Google Scholar, Web of Science, Elsevier, Springer, ACS, CNKI, and books via the keywords Guaiazulene, Matricaria chamomilla, GA-related compounds, and Guaiazulene analogous. RESULTS: The FDA has approved the bicyclic sesquiterpene GA, commonly referred to as azulon or 1,4-dimethyl-7-isopropylazulene, as a component in cosmetic colorants. The pleiotropic health advantages of GA and related substances, especially their antioxidant and anti-inflammatory effects, attracted a lot of research. Numerous studies have found that GA can help to manage various conditions, including bacterial infections, tumors, immunomodulation, expectorants, diuretics, diaphoresis, ulcers, dermatitis, proliferation, and gastritis. These conditions all involve lipid peroxidation and inflammatory response. In this review, we have covered the biomedical applications of GA. Moreover, we also emphasize the therapeutic potential of guaiazulene derivatives in pre-clinical and clinical settings, along with their underlying mechanism(s). CONCLUSION: GA and its related compounds exhibit therapeutic potential in several diseases. Still, it is necessary to investigate their potential in animal models for various other ailments and establish their safety profile. They might be a good candidate to advance to clinical trials.

The curative and mechanistic acumen of curcuminoids formulations against haloperidol induced Parkinson's disease animal model.

Parkinson's disease (PD) is slowly developing neurodegenerative disorder associated with gradual decline in cerebration and laboriousness to perform routine piece of work. PD imposed a social burden on society through higher medical cost and by loss of social productivity in current era. The available treatment options are expensive and associated with serious adverse effect after long term use. Therefore, there is a critical clinical need to develop alternative pharmacotherapies from natural sources to prevent and cure the pathological hall marks of PD with minimal cost. Our study aimed to scrutinize the antiparkinsonian potential of curcuminoids-rich extract and its binary and ternary inclusion complexes. In healthy rats, 1 mg/kg haloperidol daily intraperitoneally, for 3 weeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15-30 mg/kg, L-dopa and carbidopa (100 + 25 mg/kg) were orally administered on each day for 3 weeks. Biochemical, histopathological and RT-qPCR analyses were conducted after neurobehavioral observations. Findings of current study indicated that all curcuminoids formulations markedly mitigated the behavioral abnormalities, recovered the level of antioxidant enzymes, acetylcholinesterase inhibitory activity and neurotransmitters. Histological analysis revealed that curcuminoids supplements stabilized the neuronal loss, pigmentation and Lewy bodies' formation. The mRNA expressions of neuro-inflammatory and specific PD pathological biomarkers were downregulated by treatment with curcuminoids formulations. Therefore, it is suggested that these curcuminoids rich extract, binary and ternary supplements should be considered as promising therapeutic agents in development of modern anti-Parkinson's disease medications.

Bridging the genomic data gap in Africa: implications for global disease burdens.

This paper highlights the gap in the use of genomic data of Africans for global research efforts for disease cures. Genomic data represents an important tool used in disease research for understanding how diseases affect several populations and how these differences can be harnessed for the development of effective cures especially vaccines that have an impact at the genetic level e.g., RNA vaccines.This paper then provides a review of global genomic data status where three continents are reported to be the major contributor of genomic data to repositories used for disease research and the development of vaccines and medicines around the world.We reviewed the most recently published information about genetic data inclusiveness of populations, explaining how genomic data of Africans is lacking in global research efforts that cater towards the eradication of pandemics via the development of vaccines and other cures. We also discuss the implication of this non-inclusiveness for global disease burdens and indicate where changes need to be made in the last part of the paper.Lastly, the entire centers on some general policy recommendations to fully include African genomic data in such global genetic repositories. These recommendations can be implemented in African countries to improve genetic data collection, storage, and usage policies.

Role of Nanoparticles in Enhancing Crop Tolerance to Abiotic Stress: A Comprehensive Review.

Plants are subjected to a wide range of abiotic stresses, such as heat, cold, drought, salinity, flooding, and heavy metals. Generally, abiotic stresses have adverse impacts on plant growth and development which affects agricultural productivity, causing food security problems, and resulting in economic losses. To reduce the negative effects of environmental stress on crop plants, novel technologies, such as nanotechnology, have emerged. Implementing nanotechnology in modern agriculture can also help improve the efficiency of water usage, prevent plant diseases, ensure food security, reduce environmental pollution, and enhance sustainability. In this regard, nanoparticles (NPs) can help combat nutrient deficiencies, promote stress tolerance, and improve the yield and quality of crops. This can be achieved by stimulating the activity of certain enzymes, increasing the contents (e.g., chlorophyll) and efficiency of photosynthesis, and controlling plant pathogens. The use of nanoscale agrochemicals, including nanopesticides, nanoherbicides, and nanofertilizers, has recently acquired increasing interest as potential plant-enhancing technologies. This review acknowledges the positive impacts of NPs in sustainable agriculture, and highlights their adverse effects on the environment, health, and food chain. Here, the role and scope of NPs as a practical tool to enhance yield and mitigate the detrimental effects of abiotic stresses in crops are described. The future perspective of nanoparticles in agriculture has also been discussed.

Decorated Au NPs on lignin coated magnetic nanoparticles: Investigation of its catalytic application in the reduction of aromatic nitro compounds and its performance against human lung cancer.

In the recent years, bio-functionalized noble metal doped advanced magnetics nanocomposite materials has been materialized as potential featured catalysts in diverse applications. In this connection, we report herein a novel biogenic lignin driven Au nanoparticle supported Fe3O4 composite material. The procedure is free from any harsh reducing or stabilizing agent. Morphology and structural features were assessed following different physicochemical methodologies like FT-IR, FE-SEM, TEM, EDS, XRD, VSM and ICP-OES techniques. Thereafter, the [Fe3O4/Lignin/Au] material was successfully employed in the efficient reduction of different nitroarenes in aqueous medium. The process was monitored over UV-Vis spectroscopic study. Excellent yields were achieved with a range of diverse functionalized nitroarenes within 10-45 min of reaction. The nanocatalyst was recycled 10 times without any significant loss of catalytic activity. Distinctiveness of the material's activity was validated by comparing the results in the reduction of 4-nitrophenol. Furthermore, the prepared [Fe3O4/Lignin/Au] nanocomposite system exhibited outstanding antioxidant and anticancer effects against five lung cancer cell lines, such as, BICR 3, BICR 78, CALU 1, ChaGo-K-1, and A549. Cytotoxicity assay was determined in terms of % cell viability following MTT protocol. The corresponding IC50 values were obtained as 47, 31, 19, 25, and 31 µg/mL respectively.

Upgrading the physiochemical and sensory quality of yogurt by incorporating polyphenol-enriched citrus pomaces with antioxidant, antimicrobial, and antitumor activities.

Industrial pomaces are cheap sources of phenolic compounds and fibers but dumping them in landfills has negative environmental and health consequences. Therefore, valorizing these wastes in the food industry as additives significantly enhances the final product. In this study, the citrus pomaces, orange pomace (OP), mandarin pomace (MP), and lemon pomace (LP) were collected by a juice company and subjected to producing polyphenols and fiber-enriched fractions, which are included in functional yogurt; the pomace powder with different levels (1, 3, and 5%) was homogenized in cooled pasteurized milk with other ingredients (sugar and starter) before processing the yogurt fermentation. The HPLC phenolic profile showed higher phenolic content in OP extract, i.e., gallic acid (1,702.65), chlorogenic acid (1,256.22), naringenin (6,450.57), catechin (1,680.65), and propyl gallate (1,120.37) ppm with massive increases over MP (1.34-37 times) and LP (1.49-5 times). The OP extract successfully scavenged 87% of DPPH with a relative increase of about 16 and 32% over LP and MP, respectively. Additionally, it inhibits 77-90% of microbial growth at 5-8 µg/mL while killing them in the 9-14 µg/mL range. Furthermore, OP extract successfully reduced 77% of human breast carcinoma. Each of pomace powder sample (OP, MP, LP) was added to yogurt at three levels; 1, 3, and 5%, while the physiochemical, sensorial, and microbial changes were monitored during 21 days of cold storage. OP yogurt had the highest pH and lowest acidity, while LP yogurt recorded the reverse. High fat and total soluble solids (TSS) content are observed in OP yogurt because of the high fiber content in OP. The pH values of all yogurt samples decreased, while acidity, fat, and TSS increased at the end of the storage period. The OP yogurts 1 and 3% scored higher in color, flavor, and structure than other samples. By measuring the microbial load of yogurt samples, the OP (1 and 3%) contributes to the growth of probiotics (Lactobacillus spp) in yogurt samples and reduces harmful microbes. Using citrus pomace as a source of polyphenols and fiber in functional foods is recommended to enhance their physiochemical and sensory quality.

Plant growth-promoting microorganisms as biocontrol agents of plant diseases: Mechanisms, challenges and future perspectives.

Plant diseases and pests are risk factors that threaten global food security. Excessive chemical pesticide applications are commonly used to reduce the effects of plant diseases caused by bacterial and fungal pathogens. A major concern, as we strive toward more sustainable agriculture, is to increase crop yields for the increasing population. Microbial biological control agents (MBCAs) have proved their efficacy to be a green strategy to manage plant diseases, stimulate plant growth and performance, and increase yield. Besides their role in growth enhancement, plant growth-promoting rhizobacteria/fungi (PGPR/PGPF) could suppress plant diseases by producing inhibitory chemicals and inducing immune responses in plants against phytopathogens. As biofertilizers and biopesticides, PGPR and PGPF are considered as feasible, attractive economic approach for sustainable agriculture; thus, resulting in a "win-win" situation. Several PGPR and PGPF strains have been identified as effective BCAs under environmentally controlled conditions. In general, any MBCA must overcome certain challenges before it can be registered or widely utilized to control diseases/pests. Successful MBCAs offer a practical solution to improve greenhouse crop performance with reduced fertilizer inputs and chemical pesticide applications. This current review aims to fill the gap in the current knowledge of plant growth-promoting microorganisms (PGPM), provide attention about the scientific basis for policy development, and recommend further research related to the applications of PGPM used for commercial purposes.

The role of berberine in Covid-19: potential adjunct therapy.

Coronavirus disease 2019 (Covid-19) is a global diastrophic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 leads to inflammatory, immunological, and oxidative changes, by which SARS-CoV-2 leads to endothelial dysfunction (ED), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and multi-organ failure (MOF). Despite evidence illustrating that some drugs and vaccines effectively manage and prevent Covid-19, complementary herbal medicines are urgently needed to control this pandemic disease. One of the most used herbal medicines is berberine (BBR), which has anti-inflammatory, antioxidant, antiviral, and immune-regulatory effects; thus, BBR may be a prospective candidate against SARS-CoV-2 infection. This review found that BBR has anti-SARS-CoV-2 effects with mitigation of associated inflammatory changes. BBR also reduces the risk of ALI/ARDS in Covid-19 patients by inhibiting the release of pro-inflammatory cytokines and inflammatory signaling pathways. In conclusion, BBR has potent anti-inflammatory, antioxidant, and antiviral effects. Therefore, it can be utilized as a possible anti-SARS-CoV-2 agent. BBR inhibits the proliferation of SARS-CoV-2 and attenuates the associated inflammatory disorders linked by the activation of inflammatory signaling pathways. Indeed, BBR can alleviate ALI/ARDS in patients with severe Covid-19. In this sense, clinical trials and prospective studies are suggested to illustrate the potential role of BBR in treating Covid-19.

The Potential Role of Growth Differentiation Factor 15 in COVID-19: A Corollary Subjective Effect or Not?

Coronavirus disease 2019 (COVID-19) is primarily caused by various forms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants. COVID-19 is characterized by hyperinflammation, oxidative stress, multi-organ injury (MOI)-like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Different biomarkers are used in the assessment of COVID-19 severity including D-dimer, ferritin, lactate dehydrogenase (LDH), and hypoxia-inducible factor (HIF). Interestingly, growth differentiation factor 15 (GDF15) has recently become a potential biomarker correlated with the COVID-19 severity. Thus, this critical review aimed to determine the critical association between GDF15 and COVID-19. The perfect function of GDF15 remains not well-recognized; nevertheless, it plays a vital role in controlling cell growth, apoptosis and inflammatory activation. Furthermore, GDF15 may act as anti-inflammatory and pro-inflammatory signaling in diverse cardiovascular complications. Furthermore, the release of GDF15 is activated by various growth factors and cytokines including macrophage colony-stimulating factor (M-CSF), angiotensin II (AngII) and p53. Therefore, higher expression of GDF15 in COVID-19 might a compensatory mechanism to stabilize and counteract dysregulated inflammatory reactions. In conclusion, GDF15 is an anti-inflammatory cytokine that could be associated with the COVID-19 severity. Increased GDF15 could be a compensatory mechanism against hyperinflammation and exaggerated immune response in the COVID-19. Experimental, preclinical and large-scale clinical studies are warranted in this regard.

Chemical Profiling, Formulation Development, In Vitro Evaluation and Molecular Docking of Piper nigrum Seeds Extract Loaded Emulgel for Anti-Aging.

Emulgel is a new innovatory technique for drug development permitting controlled release of active ingredients for topical administration. We report a stable emulgel of 4% Piper nigrum extract (PNE) prepared using 80% ethanol. The PNE-loaded formulation had an antioxidant activity of 84% and tyrosinase inhibition was 82%. Prepared formulation rendered spherical-shaped globules with high zeta potential (-45.5 mV) indicative of a stable system. Total phenolic contents were 58.01 mg GAE/g of dry extract whereas total flavonoid content was 52.63 mg QE/g of dry extract. Sun protection factor for PNE-loaded emulgel was 7.512 and formulation was stable without any evidence of physical and chemical changes following 90 days of storage. Gas chromatography-mass spectroscopy (GC-MS) revealed seventeen bioactive compounds in the PNE including monoterpenoids, triterpenoids, a tertiary alcohol, fatty acid esters, and phytosterols. In silico studies of GC-MS identified compounds show higher binding affinity in comparison to standard kojic acid indicating tyrosinase inhibition. It can be concluded that PNE-loaded emulgel had prominent antioxidant and tyrosinase inhibition and can be utilized as a promising topical system for anti-aging skin formulation.

Cyclodextrin nanoparticles for diagnosis and potential cancer therapy: A systematic review.

Cancer is still one of the world's deadliest health concerns. As per latest statistics, lung, breast, liver, prostate, and cervical cancers are reported topmost worldwide. Although chemotherapy is most widely used methodology to treat cancer, poor pharmacokinetic parameters of anticancer drugs render them less effective. Novel nano-drug delivery systems have the caliber to improve the solubility and biocompatibility of various such chemical compounds. In this regard, cyclodextrins (CD), a group of natural nano-oligosaccharide possessing unique physicochemical characteristics has been highly exploited for drug delivery and other pharmaceutical purposes. Their cup-like structure and amphiphilic nature allows better accumulation of drugs, improved solubility, and stability, whereas CDs supramolecular chemical compatibility renders it to be highly receptive to various kinds of functionalization. Therefore combining physical, chemical, and bio-engineering approaches at nanoscale to specifically target the tumor cells can help in maximizing the tumor damage without harming non-malignant cells. Numerous combinations of CD nanocomposites were developed over the years, which employed photodynamic, photothermal therapy, chemotherapy, and hyperthermia methods, particularly targeting cancer cells. In this review, we discuss the vivid roles of cyclodextrin nanocomposites developed for the treatment and theranostics of most important cancers to highlight its clinical significance and potential as a medical tool.