Role of ferroptosis pathways in neuroinflammation and neurological disorders: From pathogenesis to treatment.

Ferroptosis is a newly discovered non-apoptotic and iron-dependent type of cell death. Ferroptosis mainly takes place owing to the imbalance of anti-oxidation and oxidation in the body. It is regulated via a number of factors and pathways both inside and outside the cell. Ferroptosis is closely linked with brain and various neurological disorders (NDs). In the human body, the brain contains the highest levels of polyunsaturated fatty acids, which are known as lipid peroxide precursors. In addition, there is also a connection of glutathione depletion and lipid peroxidation with NDs. There is growing evidence regarding the possible link between neuroinflammation and multiple NDs, such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and stroke. Recent studies have demonstrated that disruptions of lipid reactive oxygen species (ROS), glutamate excitatory toxicity, iron homeostasis, and various other manifestations linked with ferroptosis can be identified in various neuroinflammation-mediated NDs. It has also been reported that damage-associated molecular pattern molecules including ROS are generated during the events of ferroptosis and can cause glial activation via activating neuroimmune pathways, which subsequently leads to the generation of various inflammatory factors that play a role in various NDs. This review summarizes the regulation pathways of ferroptosis, the link between ferroptosis as well as inflammation in NDs, and the potential of a range of therapeutic agents that can be used to target ferroptosis and inflammation in the treatment of neurological disorders.

Molecular effects of Vitamin-D and PUFAs metabolism in skeletal muscle combating Type-II diabetes mellitus.

Multiple post-receptor intracellular alterations such as impaired glucose transfer, glucose phosphorylation, decreased glucose oxidation, and glycogen production contribute to insulin resistance (IR) in skeletal muscle, manifested by diminished insulin-stimulated glucose uptake. Type-2 diabetes mellites (T2DM) has caused by IR, which is also seen in obese patients and those with metabolic syndrome. The Vitamin-D receptor (VDR) and poly unsaturated fatty acids (PUFAs) roles in skeletal muscle growth, shapes, and function for combating type-2 diabetes have been clarified throughout this research. VDR and PUFAs appears to show a variety of effects on skeletal muscle, in addition it shows a promising role on bone and mineral homeostasis. Individuals having T2DM are reported to suffer from severe muscular weakness and alterations in shape of the muscle. Several studies have investigated the effect on VDR on muscular strength and mass, which leads to Vitamin-D deficiency (VDD) in individuals, in which most commonly seen in elderly. VDR has been shown to affect skeletal cellular proliferation, intracellular calcium handling, as well as genomic activity in a variety of different ways such as muscle metabolism, insulin sensitivity, which is the major characteristic pathogenesis for IR in combating T2DM. The identified VDR gene polymorphisms are ApaI, TaqI, FokI, and BsmI that are associated with T2DM. This review collates informations on the mechanisms by which VDR activation takes place in skeletal muscles. Despite the significant breakthroughs made in recent decades, various studies show that IR affects VDR and PUFAs metabolism in skeletal muscle. Therefore, this review collates the data to show the role of VDR and PUFAs in the skeletal muscles to combat T2DM.

An Integrated Computational and Experimental Approach to Formulate Tamanu Oil Bigels as Anti-Scarring Agent.

Tamanu oil has traditionally been used to treat various skin problems. The oil has wound-healing and skin-regenerating capabilities and encourages the growth of new skin cells, all of which are helpful for fading scars and hyperpigmentation, as well as promoting an all-around glow. The strong nutty odor and high viscosity are the major disadvantages associated with its application. The aim of this study was to create bigels using tamanu oil for its anti-scarring properties and predict the possible mechanism of action through the help of molecular docking studies. In silico studies were performed to analyze the binding affinity of the protein with the drug, and the anti-scarring activity was established using a full-thickness excision wound model. In silico studies revealed that the components inophyllum C, 4-norlanosta-17(20),24-diene-11,16-diol-21-oic acid, 3-oxo-16,21-lactone, calanolide A, and calophyllolide had docking scores of -11.3 kcal/mol, -11.1 kcal/mol, -9.8 kcal/mol, and -8.6 kcal/mol, respectively, with the cytokine TGF-ß1 receptor. Bigels were prepared with tamanu oil ranging from 5 to 20% along with micronized xanthan gum and evaluated for their pH, viscosity, and spreadability. An acute dermal irritation study in rabbits showed no irritation, erythema, eschar, or edema. In vivo excisional wound-healing studies performed on Wistar rats and subsequent histopathological studies showed that bigels had better healing properties when compared to the commercial formulation (MurivennaTM oil). This study substantiates the wound-healing and scar reduction potential of tamanu oil bigels.

Prevalence of Depression and Anxiety Disorders Among Cancer Patients: An Insight From a Single Institute.

Objective This cross-sectional, observational study aimed at finding the prevalence of anxiety and depression in cancer patients and the correlation of anxiety and depression with various factors, such as age, sex, marital status, educational status, occupation, financial support, duration, type of care, sort of carcinoma, and stages of malignancy, among cancer patients attending the G. Kuppuswamy Naidu Memorial Hospital, Coimbatore, Tamil Nadu, India from July 2022 to December 2022, using the Hospital Anxiety and Depression Scale (HADS). Methods A total of 162 cancer patients referred for various cancer therapies (chemo/surgery/combination therapies) were included. All patients were administered the HADS. The association between anxiety scores and various factors such as age, site, and sex was found using the chi-square test. Results Thirty-nine (24.1%) patients had severe anxiety, 60 (37%) patients had borderline anxiety, and 63 (38.9%) patients were found to be normal. Fifty-three (32.7%) patients had severe depression, 47 (29%) patients had borderline depression, and 62 (38.3%) patients were found to be normal. The findings of this study indicate that educational status and occupational status are the significant factors (p < 0.05) responsible for increasing the risk of prevalence of anxiety and depression in cancer patients. Another interesting observation in this study was that patients with breast and gastrointestinal cancer had the highest prevalence of depression among other cancer types. Conclusions The present study contributed to the prevalence of anxiety and depression in cancer patients in Tamil Nadu, India. While the study population is small, which is a limitation of the present study, it has provided an overview that educational status and occupation contribute significantly to anxiety and depression, which has not been explored much in the past. To efficiently manage this, patients should be made aware of the financial support available from various philanthropic groups, government policies, and insurance so that they can improve their quality of life and manage their clinical condition in a more confident manner. These findings call for the need for early psychiatric interventions in cancer care to improve the quality of life of patients by focusing on improving patients' mental stability and adherence to the medications for providing positive outcomes from the cancer treatments.

Celastrol: A Potential Natural Lead Molecule for New Drug Design, Development and Therapy for Memory Impairment.

Celastrol is a naturally occurring chemical isolated from Tripterygium wilfordii Hook. f., root extracts widely known for their neuroprotective properties. In this review, we focus on the efficacy of celastrol in mitigating memory impairment (MI) in both in vivo and in vitro models. Scopus, PubMed and Web of Science databases were utilised to locate pertinent literatures that explore the effects of celastrol in the brain, including its pharmacokinetics, bioavailability, behavioral effects and some of the putative mechanisms of action on memory in many MI models. To date, preclinical studies strongly suggest that celastrol is highly effective in enhancing the cognitive performance of MI animal models, particularly in the memory domain, including spatial, recognition, retention and reference memories, via reduction in oxidative stress and attenuation of neuro-inflammation, among others. This review also emphasised the challenges and potential associated enhancement of medication delivery for MI treatment. Additionally, the potential structural alterations and derivatives of celastrol in enhancing its physicochemical and drug-likeness qualities are examined. The current review demonstrated that celastrol can improve cognitive performance and mitigate MI in several preclinical investigations, highlighting its potential as a natural lead molecule for the design and development of a novel neuroprotective medication.

Chemistry, Biosynthesis and Pharmacology of Streptonigrin: An Old Molecule with Future Prospects for New Drug Design, Development and Therapy.

Streptonigrin is an aminoquinone alkaloid isolated from Streptomyces flocculus and is gaining attention as a drug molecule owing to its potential antitumor and antibiotic effects. It was previously used as an anticancer drug but has been discontinued because of its toxic effects. However, according to the most recent studies, the toxicity of streptonigrin and its structurally modified derivatives has been reduced while maintaining their potential pharmacological action at lower concentrations. To date, many investigations have been conducted on this molecule and its derivatives to determine the most effective molecule with low toxicity to enable new drug discovery. Therefore, the main objective of this study is to provide a comprehensive review and to discuss the prospects for streptonigrin and its derived compounds, which may boost the molecule as a highly interesting target molecule for new drug design, development and therapy. To complete this review, relevant literature was collected from several scientific databases, including Google Scholar, PubMed, Scopus and ScienceDirect. Following a complete screening, the obtained information is summarized in the present review to provide a good reference and accelerate the development and utilization of streptonigrin and its derivatives as pharmaceuticals.

Identification of BACE-1 Inhibitors against Alzheimer's Disease through E-Pharmacophore-Based Virtual Screening and Molecular Dynamics Simulation Studies: An Insilco Approach.

Alzheimer is a severe memory and cognitive impairment neurodegenerative disease that is the most common cause of dementia worldwide and characterized by the pathological accumulation of tau protein and amyloid-beta peptides. In this study, we have developed E-pharmacophore modeling to screen the eMolecules database with the help of a reported co-crystal structure bound with Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE-1). Flumemetamol, florbetaben, and florbetapir are currently approved drugs for use in the clinical diagnosis of Alzheimer's disease. Despite the benefits of commercially approved drugs, there is still a need for novel diagnostic agents with enhanced physicochemical and pharmacokinetic properties compared to those currently used in clinical practice and research. In the E-pharmacophore modeling results, it is revealed that two aromatic rings (R19, R20), one donor (D12), and one acceptor (A8) are obtained, and also that similar pharmacophoric features of compounds are identified from pharmacophore-based virtual screening. The identified screened hits were filtered for further analyses using structure-based virtual screening and MM/GBSA. From the analyses, top hits such as ZINC39592220 and en1003sfl.46293 are selected based on their top docking scores (-8.182 and -7.184 Kcal/mol, respectively) and binding free energy (-58.803 and -56.951 Kcal/mol, respectively). Furthermore, a molecular dynamics simulation and MMPBSA study were performed, which revealed admirable stability and good binding free energy throughout the simulation period. Moreover, Qikprop results revealed that the selected, screened hits have good drug-likeness and pharmacokinetic properties. The screened hits ZINC39592220 and en1003sfl.46293 could be used to develop drug molecules against Alzheimer's disease.

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review.

Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively.

Multilayered nanofibrous scaffold of Polyvinyl alcohol/gelatin/poly (lactic-co-glycolic acid) enriched with hemostatic/antibacterial agents for rapid acute hemostatic wound healing.

Electrospun nanofibers scaffolds show promising potential in wound healing applications. This work aims to fabricate nanofibrous wound dressing as a novel approach for a topical drug delivery system. Herein, the electrospinning technique is used to design and fabricate bioabsorbable nanofibrous scaffolds of Polyvinyl alcohol/gelatin/poly (lactic-co-glycolic acid) enriched with thrombin (TMB) as hemostatic agent and vancomycin (VCM) as anti-bacterial agent for a multifunctional platform to control excessive blood loss, inhibit bacterial growth and enhance wound healing. SEM, FTIR, XRD, in vitro drug release, antimicrobial studies, biofilm, cell viability assay, and in vivo study in a rat model were used to assess nanofiber's structural, mechanical, and biological aspects. SEM images confirms the diameter of nanofibers which falls within the range from 150 to 300 nm for all the batches. Excellent swelling index data makes it suitable to absorb wound exudates. In-vitro drug release data shows sustained release behavior of nanofiber. Nanofibers scaffolds showed biomimetic behavior and excellent biocompatibility. Moreover, scaffolds exhibited excellent antimicrobial and biofilm activity against Staphylococcus aureus. Nanofibrous scaffolds showed less bleeding time, rapid blood coagulation, and excellent wound closure in a rat model. ELISA study demonstrated the decreasing level of inflammatory markers, such as TNF-α, IL1ß, and IL-6, making formulation promising for hemostatic wound healing applications. Finally, the study concludes that nanofibrous scaffolds loaded with TMB and VCM have promising potential as a dressing material for hemostatic wound healing applications.

Development of a Polyherbal Topical Gel for the Treatment of Acne.

The present work aimed to formulate and evaluate a polyherbal gel using Aloe barbadensis and extract of Vigna radiata for the treatment of acne, a disorder of the skin in which hair follicles and sebaceous glands are blocked, causing inflammation and redness of the skin. Aloe barbadensis pulp was collected and mixed with the extract of Vigna radiata and formulated into a gel using Carbopol 940, triethanolamine, and propylene glycol as the gelling agent, viscosity modifier, and pH modifier, respectively. The gel was evaluated for its antimicrobial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans. Antimicrobial agents, such as gentamycin and fluconazole, were used as the standards. The developed formulation showed promising zone of inhibition. The gel was further evaluated for its physicochemical properties. The formulation showed a promising effect on acne together with the additive effect of Aloe barbadensis on skin.

Appraising the therapeutical potentials of Alchornea laxiflora (Benth.) Pax & K. Hoffm., an underexplored medicinal herb: A systematic review.

Ethnopharmacological relevance: Alchornea laxiflora (Benth.) Pax & K. Hoffm. (Euphorbiaceae) is an important traditional medicinal plant grown in tropical Africa. The stem, leaves, and root have been widely used in the folk medicine systems in Nigeria, Cameroon, South Africa, and Ghana to treat various ailments, including inflammatory, infectious, and central nervous system disorders, such as anxiety and epilepsy. Material and methods: The scientific name of the plant was validated using the "The Plant List," "Kew Royal Botanic Gardens," and Tropicos Nomenclatural databases. The literature search on A. laxiflora was performed using electronic search engines and databases such as Google scholar, ScienceDirect, PubMed, AJOL, Scopus, and Mendeley. Results: To the best of our knowledge, no specific and detailed review has been reported on A. laxiflora. Consequently, this review provides an up-to-date systematic presentation on ethnobotany, phytoconstituents, pharmacological activities, and toxicity profiles of A. laxiflora. Phytochemical investigations disclosed the presence of important compounds, such as alkaloids, flavonoids, phenolics, terpenoids, and fatty acids. Furthermore, various pharmacological activities and traditional uses reported for this botanical drug were discussed comprehensively. Conclusion: This systemic review presents the current status and perspectives of A. laxiflora as a potential therapeutic modality that would assist future researchers in exploring this African botanical drug as a source of novel drug candidates for varied diseases.

Baicalein prevents stress-induced anxiety behaviors in zebrafish model.

Baicalein is a flavonoid mainly obtained from plants with wide range of biological activities, including neuroprotection. An acute and unexpected chronic stress (UCS) protocol has recently been adapted to zebrafish, a popular vertebrate model in brain research. The present study was aimed to evaluate baicalein's anti-anxiety potential in a zebrafish model by induction, which included neuropharmacological evaluation to determine behavioural parameters in the novel tank diving test (NTDT) and light-dark preference test (LDPT). The toxicity was also assessed using the brine shrimp lethality assay, and the 50% lethal concentration (LC50) was determined. The animals were then stressed for 7 days before being treated with different doses of baicalein (1 and 2 mg/L) for another 7 days in UCS condition. Due to acute stress and UCS, the frequency of entries and time spent in the 1) top region and 2) light area of the novel tank reduced significantly, indicating the existence of elevated anxiety levels. The biological activity of baicalein was demonstrated by its high LC50 values (1,000 µg/ml). Additionally, baicalein administration increased the frequency of entries and duration spent in the light region, indicating a significant decrease in anxiety levels. Overall, the present results showed that baicalein has a therapeutic advantage in reversing the detrimental consequences of UCS and acute stress, making it is a promising lead molecule for new drug design, development, and therapy for stress.

Synthesis and appraisal of dalbergin-loaded PLGA nanoparticles modified with galactose against hepatocellular carcinoma: In-vitro, pharmacokinetic, and in-silico studies.

Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer via changing mRNA levels of apoptosis-related proteins. DL belongs to neoflavonoids, a drug category with low solubility and poor bioavailability. We created a synthetic version of this naturally occurring chemical, DL, and then analyzed it using 1H-NMR, 13C-NMR, and LC-MS. We also made PLGA nanoparticles and then coated them with galactose. The design of experiment software was used to optimize DL-loaded galactose-modified PLGA nanoparticles. The optimized DL-nanoformulations (DLF) and DL-modified nanoformulations (DLMF) were analyzed for particle size, polydispersity index, shape, and potential interactions. In-vitro experiments on liver cancer cell lines (HepG2) are used to validate the anti-proliferative efficacy of the modified DLMF. The in-vitro research on HepG2 cell lines also demonstrated cellular accumulation of DLF and DLMF by FITC level. The in-vitro result suggested that DLMF has high therapeutic effectiveness against HCC. In-vivo pharmacokinetics and bio-distribution experiments revealed that DLMF excelled pristine DL in terms of pharmacokinetic performance and targeted delivery, which is related to galactose's targeting activity on the asialoglycoprotein receptor (ASGPR) in hepatic cells. Additionally, we performed an in-silico study of DL on caspase 3 and 9 proteins, and the results were found to be -6.7 kcal/mol and -6.6 kcal/mol, respectively. Our in-silico analysis revealed that the DL had strong apoptotic properties against HCC.

Potential effects of noni (Morinda citrifolia L.) fruits extract against obsessive-compulsive disorder in marble burying and nestlet shredding behavior mice models.

Obsessive-compulsive disorder (OCD) is a chronic and complex psychiatric disorder that usually includes both obsessions and compulsions. Morinda citrifolia L. (Noni) is a functional food and it is a well-known plant due to its potential therapeutic effects on human health in many disorders including neurological and neurodegenerative diseases. The purpose of this study was to evaluate the potential effect of M. citrifolia fruits extract (MCFE) against obsessive-compulsive disorder using the marble burying and nestlet shredding behavior mice models. In addition, brain neurotransmitters such as dopamine (DA), serotonin and noradrenaline (NA) were also assessed. Five mice were placed in each of the different groups, and the treatment was given to the animals for a period of 15 days. The marble burying test was evaluated for 30 min on days 1, 7, and 14 while the nestlet shredding test was evaluated for 60 min on days 2, 8, and 15. Treatments with MCFE (100 and 200 mg/kg, p.o.) significantly improved in both behavior tasks when compared to the control group. In addition, diazepam (2 mg/kg, i.p.) and fluoxetine (15 mg/kg, p.o.) were also significantly improved in both tasks when compared with the control mice. Further locomotor activity study revealed that MCFE and fluoxetine did not affect the locomotor functions when compared to vehicle treated mice. In contrast, diazepam significantly decreased locomotion when compared to the control group. The significant amelioration of biogenic amines were observed in the MCFE-treated animals with increased serotonin levels. The histopathology of the brain, liver, and kidney tissues after MCFE administration revealed normal morphological structure with no signs of toxicity or abnormalities. All these results together suggest that MCFE can be a potential drug candidate for the treatment of OCD. Future research should focus on theidentification and the anti-compulsive activity of the constituents from M. citrifolia.

Recent advances in respiratory diseases: Dietary carotenoids as choice of therapeutics.

A group of bioactive, isoprenoid pigments known as carotenoids is mostly present in fruits and vegetables. Carotenoids are essential for the prevention of physiological issues, which makes maintaining excellent health easier. They are effective functional ingredients with potent health-promoting properties that are widely present in our food and linked to a decrease in the prevalence of chronic diseases, including respiratory diseases. Respiratory infections are the primary cause of death and life-threatening conditions globally, wreaking havoc on the global health system. People rely on dietary sources of carotenoids to reduce a plethora of respiratory diseases such as chronic obstructive pulmonary disease (COPD), lung cancer, asthma, and so on. Carotenoids have received a lot of interest recently in several parts of the world due to their therapeutic potential in altering the pathogenic pathways underlying inflammatory respiratory diseases, which may improve disease control and have beneficial health benefits. This review aimed to provide a thorough understanding of the therapeutic potential of dietary carotenoids in the treatment of respiratory diseases and to identify possible candidates for novel therapeutic development.

Medicinal Plants of Solanum Species: The Promising Sources of Phyto-Insecticidal Compounds.

Several medicinal plants have the potential to be a promising alternative pharmacological therapy for a variety of human illnesses. Many insects, including mosquitoes, are important vectors of deadly pathogens and parasites, which in the world's growing human and animal populations can cause serious epidemics and pandemics. Medicinal plants continue to provide a large library of phytochemicals, which can be used to replace chemically synthesized insecticides, and utilization of herbal product-based insecticides is one of the best and safest alternatives for mosquito control. Identifying new effective phyto-derived insecticides is important to counter increasing insect resistance to synthetic compounds and provide a safer environment. Solanum genus (Solanaceae family or nightshades) comprises more than 2500 species, which are widely used as food and traditional medicine. All research publications on insecticidal properties of Solanaceae plants and their phytoconstituents against mosquitoes and other insects published up to July 2020 were systematically analyzed through PubMed/MEDLINE, Scopus, EBSCO, Europe PMC, and Google Scholar databases, with focus on species containing active phytoconstituents that are biodegradable and environmentally safe. The current state of knowledge on larvicidal plants of Solanum species, type of extracts, target insect species, type of effects, name of inhibiting bioactive compounds, and their lethal doses (LC50 and LC90) were reviewed in this study. These studies provide valuable information about the activity of various species of Solanum and their phytochemical diversity, as well as a roadmap for optimizing select compounds for botanical repellents against a variety of vectors that cause debilitating and life-threatening human diseases.

Diallyl Disulfide: A Bioactive Garlic Compound with Anticancer Potential.

Cancer is a life-threatening disease caused by the uncontrolled division of cells, which culminates in a solid mass of cells known as a tumor or liquid cancer. It is the leading cause of mortality worldwide, and the number of cancer patients has been increasing at an alarming rate, with an estimated 20 million cases expected by 2030. Thus, the use of complementary or alternative therapeutic techniques that can help prevent cancer has been the subject of increased attention. Garlic, the most widely used plant medicinal product, exhibits a wide spectrum of biological activities, including antibacterial, hypo-lipidemic, antithrombotic, and anticancer effects. Diallyl disulfide (DADS) is a major organosulfur compound contained within garlic. Recently, several experimental studies have demonstrated that DADS exhibits anti-tumor activity against many types of tumor cells, including gynecological cancers (cervical cancer, ovarian cancer), hematological cancers (leukemia, lymphoma), lung cancer, neural cancer, skin cancer, prostate cancer, gastrointestinal tract and associated cancers (esophageal cancer, gastric cancer, colorectal cancer), hepatocellular cancer cell line, etc. The mechanisms behind the anticancer action of DADS include epithelial-mesenchymal transition (EMT), invasion, and migration. This article aims to review the available information regarding the anti-cancer potential of DADS, as well as summarize its mechanisms of action, bioavailability, and pharmacokinetics from published clinical and toxicity studies.

Investigating forthcoming strategies to tackle deadly superbugs: current status and future vision.

INTRODUCTION: Superbugs are microorganisms that cause disease and have increased resistance to the treatments typically used against infections. Recently, antibiotic resistance development has been more rapid than the pace at which antibiotics are manufactured, leading to refractory infections. Scientists are concerned that a particularly virulent and lethal 'superbug' will one day join the ranks of existing bacteria that cause incurable diseases, resulting in a global health disaster on the scale of the Black Death. AREAS COVERED: This study highlights the current developments in the management of antibiotic-resistant bacteria and recommends strategies for further regulating antibiotic-resistant microorganisms associated with the healthcare system. This review also addresses the origins, prevalence, and pathogenicity of superbugs, and the design of antibacterial against these growing multidrug-resistant organisms from a medical perspective. EXPERT OPINION: It is recommended that antimicrobial resistance should be addressed by limiting human-to-human transmission of resistant strains, lowering the use of broad-spectrum antibiotics, and developing novel antimicrobials. Using the risk-factor domains framework from this study would assure that not only clinical but also community and hospital-specific factors are covered, lowering the chance of confounders. Extensive subjective research is necessary to fully understand the underlying factors and uncover previously unexplored areas.

Development of Polymeric-Based Formulation as Potential Smart Colonic Drug Delivery System.

Conventional oral formulations are mainly absorbed in the small intestine. This limits their use in the treatment of some diseases associated with the colon, where the drug has to act topically at the inflammation site. This paved the way for the development of a smart colonic drug delivery system, thereby improving the therapeutic efficacy, reducing the dosing frequency and potential side effects, as well as improving patient acceptance, especially in cases where enemas or other topical preparations may not be effective alone in treating the inflammation. In healthy individuals, it takes an oral medication delivery system about 5 to 6 h to reach the colon. A colonic drug delivery system should delay or prohibit the medication release during these five to six hours while permitting its release afterward. The main aim of this study was to develop a smart drug delivery system based on pH-sensitive polymeric formulations, synthesized by a free-radical bulk polymerization method, using different monomer and crosslinker concentrations. The formulations were loaded with 5-amino salicylic acid as a model drug and Capmul MCM C8 as a bioavailability enhancer. The glass transition temperature (Tg), tensile strength, Young's modulus, and tensile elongation at break were all measured as a part of the dried films' characterization. In vitro swelling and release studies were performed to assess the behavior of the produced formulations. The in vitro swelling and release evaluation demonstrated the potential ability of the developed system to retard the drug release at conditions mimicking the stomach and small intestine while triggering its release at conditions mimicking the colon, which indicates its promising applicability as a potential smart colonic drug delivery system.

Synbiotic Effects of Fermented Rice on Human Health and Wellness: A Natural Beverage That Boosts Immunity.

Fermented foods have been an important component of the human diet from the time immemorial. It contains a high amount of probiotics that have been associated to a wide range of health benefits, including improved digestion and immunity. This review focuses on the indigenously prepared prebiotic- and probiotic-containing functional fermented rice (named Xaj-pani) by the Ahom Community from Assam, in Northeast India, including all the beneficial and potential effects on human health. Literature was searched from scientific databases such as PubMed, ScienceDirect and Google Scholar. Glutinous rice (commonly known as bora rice of sali variety) is primarily employed to prepare beverages that are recovered through the filtration process. The beer is normally consumed during religious rites, festivals and ritual practices, as well as being used as a refreshing healthy drink. Traditionally, it is prepared by incorporating a variety of medicinal herbs into their starter culture (Xaj-pitha) inoculum which is rich in yeasts, molds and lactic acid bacteria (LAB) and then incorporated in alcoholic beverage fermentation. The Ahom communities routinely consume this traditionally prepared alcoholic drink with no understanding of its quality and shelf life. Additionally, a finally produced dried cake, known as vekur pitha act as a source of Saccharomyces cerevisiae and can be stored for future use. Despite the rampant use in this community, the relationship between Xaj-pani's consumption, immunological response, infectious and inflammatory processes remains unknown in the presence of factors unrelated or indirectly connected to immune function. Overall, this review provides the guidelines to promote the development of prebiotic- and probiotic-containing functional fermented rice that could significantly have an impact on the health of the consumers.