Cell-Mediated Immune Response Against Mycobacterium tuberculosis and Its Potential Therapeutic Impact.

Cell-mediated immune response is critical for Mycobacterium tuberculosis (M.tb) control. Understanding of pathophysiology and role played by different cell mediators is essential for vaccine development and better management of patients with M.tb. A complex array of cytokines and chemokines are involved in the immune response against M.tb; however, their relative contribution in protection remains to be further explored. The purpose of this review is to summarize the current understanding regarding the cytokine and chemokine profiles in M.tb infection in order to assist research in the field to pursue new direction in prevention and control. We have also summarized recent findings on vaccine trials that have been developed and or are under trials that are targeting these molecules.

Exploring laccase: a sustainable enzymatic solution for the paper recycling domain.

The global advocacy of resource conservation and waste management emphasizes the significance of sustainable practices, particularly in sectors such as paper manufacturing and recycling. Currently, conventional chemical methods are predominant for paper production, necessitating the use of substantial amount of toxic chemicals. This chemical-intensive approach compromises the recycled fiber quality, generates hazardous effluent causing serious ecological threats which triggers regulatory complexities for the mills. To address these challenges modern research suggests adopting sustainable eco-friendly practices such as employing enzymes. This review aims to explore the applicability of 'laccase' enzyme for paper recycling, investigating its properties and contribution to improved recycling practices. By delving into the potential application of laccase integration into the papermaking process, this article sheds light on the limitations inherent in traditional methods surmounted within both research and translational landscapes. Culture and process optimization studies, supporting the technological improvements and the future prospects have been documented.

Diabetes: a review of its pathophysiology, and advanced methods of mitigation.

Diabetes mellitus (DM) is a long-lasting metabolic non-communicable disease often characterized by an increase in the level of glucose in the blood or hyperglycemia. Approximately, 415 million people between the ages of 20 and 79 years had DM in 2015 and this figure will rise by 200 million by 2040. In a study conducted by CARRS, it's been found that in Delhi the prevalence of diabetes is around 27% and for prediabetic cases, it is more than 46%. The disease DM can be both short-term and long-term and is often associated with one or more diseases like cardiovascular disease, liver disorder, or kidney malfunction. Early identification of diabetes may help avoid catastrophic repercussions because untreated DM can result in serious complications. Diabetes' primary symptoms are persistently high blood glucose levels, frequent urination, increased thirst, and increased hunger. Therefore, DM is classified into four major categories, namely, Type 1, Type 2, Gestational diabetes, and secondary diabetes. There are various oral and injectable formulations available in the market like insulin, biguanides, sulphonylureas, etc. for the treatment of DM. Recent attention can be given to the various nano approaches undertaken for the treatment, diagnosis, and management of diabetes mellitus. Various nanoparticles like Gold Nanoparticles, carbon nanomaterials, and metallic nanoparticles are some of the approaches mentioned in this review. Besides nanotechnology, artificial intelligence (AI) has also found its application in diabetes care. AI can be used for screening the disease, helping in decision-making, predictive population-level risk stratification, and patient self-management tools. Early detection and diagnosis of diabetes also help the patient avoid expensive treatments later in their life with the help of IoT (internet of medical things) and machine learning models. These tools will help healthcare physicians to predict the disease early. Therefore, the Nano drug delivery system along with AI tools holds a very bright future in diabetes care.

Emergence of slip-ideal-slip behavior in tip-links serve as force filters of sound in hearing.

Tip-links in the inner ear convey force from sound and trigger mechanotransduction. Here, we present evidence that tip-links (collectively as heterotetrameric complexes of cadherins) function as force filters during mechanotransduction. Our force-clamp experiments reveal that the tip-link complexes show slip-ideal-slip bond dynamics. At low forces, the lifetime of the tip-link complex drops monotonically, indicating slip-bond dynamics. The ideal bond, rare in nature, is seen in an intermediate force regime where the survival of the complex remains constant over a wide range. At large forces, tip-links follow a slip bond and dissociate entirely to cut-off force transmission. In contrast, the individual tip-links (heterodimers) display slip-catch-slip bonds to the applied forces. While with a phenotypic mutant, we showed the importance of the slip-catch-slip bonds in uninterrupted hearing, our coarse-grained Langevin dynamics simulations demonstrated that the slip-ideal-slip bonds emerge as a collective feature from the slip-catch-slip bonds of individual tip-links.

Chemical characteristics, morphology and source apportionment of PM10 over National Capital Region (NCR) of India.

The present study frames the physico-chemical characteristics and the source apportionment of PM10 over National Capital Region (NCR) of India using the receptor model's Positive Matrix Factorization (PMF) and Principal Momponent Mnalysis/Absolute Principal Component Score-Multilinear Regression (PCA/APCS-MLR). The annual average mass concentration of PM10 over the urban site of Faridabad, IGDTUW-Delhi and CSIR-NPL of NCR-Delhi were observed to be 195 ± 121, 275 ± 141 and 209 ± 81 µg m-3, respectively. Carbonaceous species (organic carbon (OC), elemental carbon (EC) and water-soluble organic carbon (WSOC)), elemental constituents (Al, Ti, Na, Mg, Cr, Mn, Fe, Cu, Zn, Br, Ba, Mo Pb) and water-soluble ionic components (F-, Cl-, SO42-, NO3-, NH4+, Na+, K+, Mg2+, Ca2+) of PM10 were entrenched to the receptor models to comprehend the possible sources of PM10. The PMF assorted sources over Faridabad were soil dust (SD 15%), industrial emission (IE 14%), vehicular emission (VE 19%), secondary aerosol (SA 23%) and sodium magnesium salt (SMS 17%). For IGDTUW-Delhi, the sources were SD (16%), VE (19%), SMS (18%), IE (11%), SA (27%) and VE + IE (9%). Emission sources like SD (24%), IE (8%), SMS (20%), VE + IE (12%), VE (15%) and SA + BB (21%) were extracted over CSIR-NPL, New Delhi, which are quite obvious towards the sites. PCA/APCS-MLR quantified the similar sources with varied percentage contribution. Additionally, catalogue the Conditional Bivariate Probability Function (CBPF) for directionality of the local source regions and morphology as spherical, flocculent and irregular were imaged using a Field Emission-Scanning Electron Microscope (FE-SEM).

Polyherbal formulation PL02 alleviates pain, inflammation, and subchondral bone deterioration in an osteoarthritis rodent model.

Introduction: Osteoarthritis (OA) is a debilitating disease with significant personal and socioeconomic burdens worldwide. Methods: To address this, we developed a multitargeted formulation called PL02, which includes standardized extracts of Rosa canina L, Hippophae rhamnoides, and collagen peptide. We tested the pharmacological efficacy of PL02 in a rodent model of OA induced by Monosodium iodoacetate (MIA). Results: Our results demonstrate that oral administration of PL02 has antioxidant effects by down-regulating NOS, reduces pain-related behavior, and mitigates inflammation by inhibiting IL-1b and TNF-α production, as well as downregulating CGRP1 and COX-II. PL02 also exhibits anti-catabolic and chondroprotective activity by significantly downregulating MMP13 and upregulating BCL2. Additionally, PL02 demonstrates chondrogenic activity by significantly upregulating SOX-9 (a master regulator of chondrogenesis), Coll-I, and aggrecan, which are major components of articular cartilage. Furthermore, PL02 prevents microarchitectural deterioration of subchondral bone. Conclusion: Overall, PL02 is an orally active, multi-targeted therapy that not only alleviates pain and inflammation but also effectively halts cartilage and subchondral bone deterioration. It represents a safe and promising candidate for the treatment and management of OA.

Albumin Nanoparticles Surface Decorated with a Tumor-Homing Peptide Help in Selective Killing of Triple-Negative Breast Cancer Cells.

In this article, we describe a method of delivery of doxorubicin using a novel tumor-homing peptide-based albumin nanoparticle system to triple-negative breast cancer cells (TNBC). The absence and reduced expression of the hormone (estrogen, progesterone) and HER2 (human epidermal growth factor 2) receptors, respectively, render TNBC patients nonsusceptible to different available targeted therapies. These peptide-modified nanoparticles could be taken up by TNBC cells more effectively than their bare counterparts. The drug-loaded peptide-modified nanoparticles achieved an optimal but crucial balance between cell killing in cancerous cells and cell survival in the noncancerous ones. This appears to be because of different routes of entry and subsequent fate of the bare and peptide-modified nanoparticles in cancerous and noncancerous cells. In a TNBC mouse model, the peptide-modified system fared better than the free drug in mounting an antitumor response while not being toxic systemically.

Overlapping imaging features between miscarriage of a low-lying gestational sac and cervical ectopic pregnancy.

Early pregnancy ultrasound must satisfy objective criteria to make a safe diagnosis of miscarriage. The differential diagnosis of low-lying gestational sac includes cervical stage of miscarriage and cervical and caesarean scar ectopic pregnancies. Misdiagnosis can lead to significant maternal morbidity. We describe a pregnancy in a 36-year-old primiparous woman where ultrasound findings of a low-lying gestation sac satisfied criteria for miscarriage; however, dilatation and curettage of pregnancy contents resulted in brisk cervical bleeding. Ultrasound at 6 weeks 6 days of gestation showed an intra-uterine pregnancy of uncertain viability. Repeat scan after 11 days confirmed miscarriage based on an absence of interval progression between scans and no embryonic heartbeat. The collapsed gestational sac (GS) was seen at the level of the internal os with decidual reaction and peri-trophoblastic blood flow. Inferior to the sac, minimally vascular trophoblastic appearing tissue was beginning to distend the upper cervical canal: the sliding sign was positive for the GS and negative for the upper cervical contents. Cervical stroma was clearly seen circumferential to the distending tissue. The patient underwent dilatation and curettage of the uterus complicated by 2000 ml haemorrhage requiring blood transfusion and medical and surgical management with intra-cavitary placement of a Foley catheter. Histopathology confirmed pregnancy tissue with the disruption of cervical epithelium but no true invasion. The patient was counselled to attend a specialist obstetric imaging facility for an early dating ultrasound in future pregnancies. The current body of literature does not describe cases of low-lying gestation sac miscarriage with high-risk features of trophoblastic extension into the cervical canal. We suggest maintaining a high index of suspicion and excluding differential diagnoses as the majority of women have no risk factors for ectopic pregnancy. These cases should be recommended for surgical management.

Bidirectional Effect of Triphala on Modulating Gut-Brain Axis to Improve Cognition in the Murine Model of Alzheimer's Disease.

SCOPE: The emerging role of gut microbiota and their metabolites in the modulation of the gut-brain axis has received much attention as a new hope for the treatment of hard-to-treat chronic neurodegenerative diseases like Alzheimer's disease. The naturally occurring polyphenols can restore the gut-brain axis by modulating gut microbiota and brain neurotransmitters. The Indian traditional medicine Triphala, a rich source of polyphenols, has been used on humans based on Prakriti or disease conditions for many years. METHODS AND RESULTS: In this study, the dual mode (morning and evening) action of Triphala is used to provide scientific evidence of its superior preventive and therapeutic efficacy in C57BL/6 and 5xFAD, APP/PS1 transgenic mouse model of Alzheimer's disease. The study observes that Triphala treatment has significantly improved cognitive function, by modulating the APP pathway, reducing inflammation, and restoring the gut-brain axis by increasing the gut microbiota phyla of Bacteroides, Proteobacteria, Actinobacteria, etc., involved in maintaining the gut homeostasis. CONCLUSIONS: The study paves a new path for using dual modes of Triphala alone or in combination to treat incurable AD.

Pulmonary Tuberculosis in Severely Malnourished Children Admitted to Nutrition Rehabilitation Centers: A Multicenter Study.

OBJECTIVES: To identify prevalence of pulmonary tuberculosis (TB) in severely malnourished children admitted to nutritional rehabilitation centers. METHODS: A multicenter cross-sectional study involving 41 nutrition rehabilitation centres (NRCs) across India was carried out to document prevalence of pulmonary tuberculosis in acute severe malnourished children admitted in NRCs. After training of the NRC staff to follow algorithm provided by national tuberculosis elimination program, children admitted to NRCs were screened for pulmonary tuberculosis. RESULTS: A total of 4356 children were enrolled across all the sites. Gastric aspirate for Cartridge based nucleic acid amplification test (CBNAAT), tuberculin skin test (TST) and X-ray film of chest were done in more than 99% of enrolled subjects. A total of 189 children (4.3%) had pulmonary tuberculosis. Eighty-seven (1.99%) were microbiologically confirmed by positive CBNAAT. On multivariate analysis, only significant association was with history of contact with TB patient in family. CONCLUSIONS: The present results suggest that a significant proportion (>4%) of children admitted in NRCs suffer from pulmonary tuberculosis. It is feasible to improve diagnosis of tuberculosis as a whole and microbiologically confirmed TB.

ARL6IP5 Ameliorates α-Synuclein Burden by Inducing Autophagy via Preventing Ubiquitination and Degradation of ATG12.

Recent advanced studies in neurodegenerative diseases have revealed several links connecting autophagy and neurodegeneration. Autophagy is the major cellular degradation process for the removal of toxic protein aggregates responsible for neurodegenerative diseases. More than 30 autophagy-related proteins have been identified as directly participating in the autophagy process. Proteins regulating the process of autophagy are much more numerous and unknown. To address this, in our present study, we identified a novel regulator (ARL6IP5) of neuronal autophagy and showed that the level of ARL6IP5 decreases in the brain with age and in Parkinson's disease in mice and humans. Moreover, a cellular model of PD (Wild type and A53T mutant α-synuclein overexpression) has also shown decreased levels of ARL6IP5. ARL6IP5 overexpression reduces α-synuclein aggregate burden and improves cell survival in an A53T model of Parkinson's disease. Interestingly, detailed mechanistic studies revealed that ARL6IP5 is an autophagy inducer. ARL6IP5 enhances Rab1-dependent autophagosome initiation and elongation by stabilizing free ATG12. We report for the first time that α-synuclein downregulates ARL6IP5 to inhibit autophagy-dependent clearance of toxic aggregates that exacerbate neurodegeneration.

Design, Synthesis, Molecular Docking Study and Biological Evaluation of Novel γ-Carboline Derivatives of Latrepirdine (Dimebon) as Potent Anticancer Agents.

A series of novel γ-Carboline derivatives were designed and synthesized using the Suzuki coupling reaction to identify the leads for the activity against cancer. Interestingly, these compounds were tested for their anticancer activity against the cell lines, particularly human cancer cell lines MCF7 (breast), A549 (lung), SiHa (cervix), and Colo-205 (colon). Most of the γ-Carboline derivatives showed potent inhibitory activity in four cancer cell lines, according to in vitro anticancer activity screening. Two compounds, specifically LP-14 and LP-15, showed superior activity in cancer cell lines among the γ-Carboline derivatives from LP-1 to LP-16. Additionally, the compound LP-14, LP-15 and Etoposide carried out molecular docking studies on human topoisomerase II beta in complex with DNA and Etoposide (PDB ID: 3QX3). The docking studies' results showed that the derivative LP-15 was strongly bound with the receptor amino acid residues, including Glu477 and DC8 compared with the marked drug Etoposide.

Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Dual mode of Triphala in the reversal of cognition through gut restoration in antibiotic mediated prolonged dysbiosis condition in 5XFAD mice.

The emerging role of gut-brain axis decoding recently created a new hope for investigating the biological and physiological basis of neurodegenerative disorders and other neurological problems. In this context, we used the bidirectional polyphenols-rich Triphala against the antibiotics cocktail-treated 5XFAD mice to decode the gut-brain axis. After 60 days of orally given Triphala and Antibiotics, the treated group showed significant improvement in the cognitive parameters in the behavioral study Morris water and Y maze. The Triphala treated group showed the neurogenesis, reduced level of amyloid beta in serum, and amyloid precursor protein, mRNA expression in the brain of mice. The serum level and mRNA expression of anti-inflammatory and antioxidant activity were also studied. Simultaneously, the Triphala-treated group showed improved gut transition time and increased butyrate levels in feces. The 16 s rRNA analysis of the V3-V4 region of feces DNA showed more presence of disease-modifying bacteria like Bacteriodetes and Verrucomicrobiota by the percentage of 31 and 23%. The reduction level in percentage abundance of Cyanobacteria indicated the effect of Triphala against AD. The availabilities of these bacteria, and the reversal of cognitive parameters in the AD mice, showed the promising effect of Triphala for treating neurodegenerative disorders.

Evidence-Based Guidelines for the Management of Allergic Bronchopulmonary Aspergillosis (ABPA) in Children and Adolescents with Asthma.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) frequently complicates asthma. There is urgent need to develop evidence-based guidelines for the management of ABPA in children. The Evidence Based Guideline Development Group (EBGDG) of the Indian Academy of Pediatrics (IAP) National Respiratory Chapter (NRC) addressed this need. METHODS: The EBGDG shortlisted clinical questions relevant to the management of ABPA in asthma. For each question, the EBGDG undertook a systematic, step-wise evidence search for existing guidelines, followed by systematic reviews, followed by primary research studies. The evidence was collated, critically appraised, and synthesized. The EBGDG worked through the Evidence to Decision (EtD) framework, to formulate recommendations, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Seven clinical questions were prioritized, and the following recommendations formulated. (1) Children with poorly controlled asthma should be investigated for ABPA (conditional recommendation, moderate certainty of evidence). (2) Low dose steroid therapy regimen (0.5 mg/kg/d for the first 2 wk, followed by a progressive tapering) is preferable to higher dose regimens (conditional recommendation, very low certainty of evidence). (3) Oral steroid regimens longer than 16 wk (including tapering), should not be used (conditional recommendation, very low certainty of evidence). (4) Antifungals may or may not be added to steroid therapy as the evidence was neither in favour nor against (conditional recommendation, low certainty of evidence). (5) For clinicians using antifungal agents, the EBGDG recommends against using voriconazole instead of itraconazole (conditional recommendation, very low certainty of evidence). (6) No evidence-based recommendation could be framed for using pulse steroid therapy in preference to conventional steroid therapy. (7) Immunotherapy with biologicals including omalizumab or dupilumab is not recommended (conditional recommendation, very low certainty of evidence). CONCLUSIONS: This evidence-based guideline can be used by healthcare providers in diverse clinical settings.

Effect of time, temperature and pH on Mycobacterium tuberculosis culture positivity of gastric aspirate: An experimental study.

BACKGROUND: The culture of gastric aspirate (GA) has been used for bacteriological confirmation of pulmonary tuberculosis in children and patients who are unable to expectorate. Sodium bicarbonate neutralization of gastric aspirates is commonly recommended to increase culture positivity. We aim to study Mycobacterium tuberculosis (MTB) culture positivity of GA collected from confirmed case of pulmonary tuberculosis after storing it at different temperature, pH & time. METHODS: GA specimens from 865 patients of either sex predominately non-expectorating children/adults with suspected pulmonary TB were collected. Gastric lavage was performed in the morning after an overnight fasting (at least 6hrs fasting). The GA specimens were tested by CBNAAT (GeneXpert) and AFB microscopy & those who were positive on CBNAAT were further processed with MTB culture on Growth Indicator Tube (MGIT™) culture. pH neutralized and non-neutralized CBNAAT positive GA specimens were culture within 2 hours of collection and 24 hours after storage at 4 °C & room temperature. RESULTS: MTB was detected in 6.8% of collected GA specimens by CBNAAT. Culture positivity of neutralized GA specimens when processed within 2 hours of collection, was higher compared to paired non-neutralized GA specimens. Neutralized GA specimens had higher contamination rate than non-neutralized GA specimens. Storage of GA specimens at $Deg C had better culture yield than those stored at room temperature. CONCLUSION: Early neutralization of acid in Gastric aspirate (GA) is essential for better culture positivity of M. tuberculosis (MTB). If there is a delay in processing GA, it should be kept at 4 °C after neutralization; however, positivity decreases with time.

Melanocyte Adhesion and Apoptosis in Vitiligo: Linking Puzzle Blocks.

Vitiligo is the utmost common depigmenting condition consequential from melanocyte loss from the basal layer of the epidermis. Vitiligo disease mostly affects dark-skinned races and makes them more sensitive to UV radiation. It is also linked with some autoimmune diseases and various psychosocial difficulties. Melanocyte loss leads to depigmentation in vitiligo, is a major concern over decades, and even affects an individual's day-to-day life severely. All the theories, including autoimmune, autocytotoxic, and neural, collectively decipher either prime impact on the melanogenesis inhibition or deficient adhesion inspired melanocytes disappearance. Previously it has been described that melanocyte loss in vitiligo patients is caused by defective adhesion. Melanocyte death by apoptosis mainly occurs due to melanocyte detachment or migration from the basal layer and further followed by transepidermal migration. Various cell surface molecules, i.e., cell adhesion molecules (CAMs) in affiliation with neighbouring cells and extracellular matrix (ECM), encompass a typical cell adhesion process. All these ECM molecules along with transcription factors, help in the survival and maintenance of pigmentary cells/melanocytes. Therefore, in this issue, we have tried to compile the literature available on melanocyte detachment/apoptosis in ECM due to the alteration in adhesion molecules and matrix metalloproteinases (MMPs) driven by known/unknown transcription factors.

Elucidating the antifungal activity and mechanism of action of bioactive phytochemicals against fungal dermatitis isolates.

Dermatophytosis has been the most common cause of superficial fungal infections which invade the keratinized tissues of body such as nail, hair, and skin, respectively. Although these infections are treatable and many commercial drugs are available that can be applied topically (clotrimazole, fluconazole, itraconazole, miconazole, voriconazole) on the infected areas but they have very low efficacy and has high probability of relapse. To increase the efficacy of treatment, the patient receives supplementary oral medicines for prolong duration that leads to hepatotoxicity. Previously, it has been reported that some wild medicinal plants possess antifungal capacity due to the presence of bioactive molecules. In present study, these phytochemicals (viz. tannins, saponins, alkaloids, flavonoids) derived from three test plants [Acacia nilotica (babul), Catharanthus roseus (sadabahar) and Ricinus communis (Arandi)] are used as sources of direct medicinal agents to develop an antidermatophytic drug formulation against the clinical fungal isolates associated with affected population. The mechanism of their antifungal potential of partially purified phytochemicals were analyzed using agar well diffusion method, food inhibition assessment and DNA cleavage analysis. The data revealed that the alkaloids are the most potent component possessing antifungal property that is recommended to be used to formulate topical ointment for the dermatophytic infection after competent regulatory approvals. This can be used as promising source of alternative treatment approach and as a competent substitute for chemically synthesized hepatotoxic drugs that are available in market.

AdipoRon induces AMPK activation and ameliorates Alzheimer's like pathologies and associated cognitive impairment in APP/PS1 mice.

Alzheimer's disease (AD) is a progressive devastating neurodegenerative disorder characterized by extracellular amyloid beta (Aß42) plaque formation, hyperphosphorylation of tau protein leading to intracellular neurofibrillary tangle formation. Recently discovered hallmark features responsible for AD pathogenesis are neuronal insulin resistance, dysregulation in adiponectin and AMPK signaling. The presence of adiponectin and its receptor in the brain with its unique anti-diabetic effects and association with neurodegenerative diseases has raised our interest in exploring orally active small molecule adiponectin receptor agonist, AdipoRon. To date, all the available drugs for the treatment of AD provides symptomatic relief and do not stall the progression of the disease. Indeed, it is becoming increasingly apparent to find appropriate targets. Here, we attempt to shed lights on adiponectin receptor agonist, AdipoRon and its downstream molecular targets in reducing disease pathogenesis and insulin resistance. In brain, AdipoRon induced AMPK activation, increased insulin sensitivity, reduced amyloid beta plaque deposition and improved cognitive impairment. Levels of BACE were also downregulated while LDLR, APOE and neprilysin were upregulated promoting amyloid beta clearance from brain. AdipoRon further reduced the chronic inflammatory marker, GFAP and improved synaptic markers PSD-95 and synaptophysin in APP/PS1 mice. Our in-vitro studies further confirmed the potential role of AdipoRon in improving insulin sensitivity by increasing GLUT 4 translocation, glucose uptake and insulin signaling under hyperinsulinemic condition. Our findings suggest that AdipoRon could be a promising lead in the future treatment strategies in the development of effective AD treatment.

Protective manifestation of herbonanoceuticals as antifungals: A possible drug candidate for dermatophytic infection.

Background and Aims: Fungal dermatophytosis or Tinea is a predominance in about 20%-25% of all total world populations. Dermatophyte infections are mainly caused by fungi belonging to Trichophyton, Epidermophyton, and Microsporum genera along with some other fungi. This epidemiological distribution may change with migration, lifestyle, immunosuppressive state, drug therapy, and socioeconomic conditions. Methods: The present review indicated the bioefficacy of herbal and herbonanoconjugate as safe management of fungal dermatophytic infection. Results: It also emphasized the action mechanism as fungicidal and fungistatic with different harmful impacts indicating the need for alternative therapeutics. Simultaneously, the herbal and herbonanoconjugate approaches proved better to manage the prevalence of hepatotoxicity, nephrotoxicity, nausea, altered taste, anemia, GI upsets, hair loss, and so forth. due to conventional oral treatment approaches. Conclusion: Adoption of the remedial approach can be recommended after preclinical trials' approval as a safe treatment.