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Raghuram Kandimalla,1 Suvakanta Dash,2 Ashim Chandra Bhowal,3 Sanjeeb Kalita,1 Narayan Chandra Talukdar,1 Sarathi Kundu,3 Jibon Kotoky1,4 1Drug Discovery Lab, Institute of Advanced Study in Science and Technology, 2Girijananda Choudhury Institute of Pharmaceutical Sciences, 3Soft Nano Laboratory, Institute of Advanced Study in Science and Technology, 4National Institute of Pharmaceutical Education and Research, Guwahati, India Abstract: In this study, a glycogen–gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV–Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl4-induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1β and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma Cmax supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly. Keywords: silymarin, Annona reticulata, glycogen–gold, nanohybrid, potency, hepatoprotection

Sanjeeb Kalita,1 Banasmita Devi,1 Raghuram Kandimalla,1 Kaustav Kalyan Sharma,1 Arup Sharma,2 Kasturi Kalita,3 Amal Chandra Kataki,4 Jibon Kotoky1 1Institute of Advanced Study in Science and Technology (IASST), Division of Life Sciences, Paschim Boragaon, Garchuk, Guwahati, Assam, India; 2College of Veterinary Science, Assam Agriculture University, Khanapara, Guwahati, Assam, India; 3Hyat Hospital, Lalganesh, Guwahati, Assam, India; 4Dr B Borooah Cancer Institute, Guwahati, Assam, India Abstract: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infection has increased precipitously over the past several decades, with far-reaching health care and societal costs. MRSA infections in the context of burn wounds lead to invasive disease that could potentially cause mortality. Chloramphenicol is a well-known broad-spectrum bacteriostatic antibiotic that has been used since 1949, but due to its hydrophobicity, poor penetration in skin, fast degradation, and toxicity, its application has been hindered. Furthermore, it has been demonstrated that old antibiotics such as chloramphenicol remained active against a large number of currently prevalent resistant bacterial isolates due to their low-level use in the past. Recently, the novel nanoparticulate drug-delivery system has been used and reported to be exceptionally useful for topical therapeutics, due to its distinctive physical characteristics such as a high surface-to-volume ratio and minuscule size. It helps to achieve better hydrophilicity, bioavailability, and controlled delivery with enhanced therapeutic index, which has resulted in decreased toxicity levels compared to the crude drug. Here, we report a novel chloramphenicol loaded with poly(ε-caprolactone) (PCL)-pluronic composite nanoparticles (CAM-PCL-P NPs), physicochemical characterizations, and its bioactivity evaluation in a MRSA-infected burn-wound animal model. CAM-PCL-P NPs could encapsulate 98.3% of the drug in the nanoparticles and release 81% of the encapsulated drug over 36 days with a time to 50% drug release of 72 hours (51%). Nanoparticle suspensions maintained the initial properties with respect to size and encapsulation efficiency, even after 6 months of storage at 4°C and 25°C, respectively (P>0.05). Significant reduction in the level of toxicity was observed for CAM-PCL-P NPs compared with that of free drug as confirmed from hemolytic activity against human blood erythrocytes and cytotoxicity assay against an MCF-7 breast cancer cell line. In vitro antibacterial activities were performed by zone of inhibition, minimum inhibitory concentrations, minimum bacterial concentration, and time-kill assays, which showed that CAM-PCL-P NPs exhibited significantly enhanced anti-MRSA activity against ten clinical isolates of MRSA strains. The augmented activity of CAM-PCL-P NPs was further tested on a MRSA-infected burn-wound animal model and achieved quicker efficacy in MRSA clearance and improved the survival rate compared with free-chloramphenicol treatment. Thus, we propose CAM-PCL-P NPs as a promising novel antimicrobial candidate that may have a good potential for preclinical applications. Keywords: chloramphenicol, PCL-pluronic, nanoparticle, methicillin-resistant Staphylococcus aureus, anti-MRSA activity, burn-wound animal model

Background: Remedial teaching is a tailored educational approach dedicated to enhancing the academic performance of students facing challenges within the curriculum. By identifying and addressing specific learning difficulties, it provides essential support and guidance to bring students closer to expected standards while preventing future setbacks. We hypothesize that underperforming medical students who receive daily, tailored remediation will demonstrate significant improvement in their formative and summative assessment scores in biochemistry., Methods: A cross-sectional mixed-method study was conducted on 56 underperforming first-year medical undergraduates to assess the effect of targeted remediation on formative and summative assessments in Biochemistry. Training sessions included various remediation techniques over six months. Post-remediation feedback was collected to gather insights into students' attitudes, perceptions, and the effectiveness of the methods in improving their understanding of the subject. Logistic regression analysis was employed to determine the most effective remediation for student performance. Benefits and weaknesses of remedial training approaches for future application as perceived by the students were derived through deductive thematic analysis of their feedback., Results: The mean marks, evaluated out of a maximum of 100, showed improvement from 29.86 ± 7.71 to 71.48 ± 10.19, with statistical significance (p < 0.001). From the students' perspective, the most effective remediation method was grade incentives in formative assessments (odds ratio 6.19). Five major themes were identified: perceived barriers prior to remediation, positive outcomes and behavioral changes observed after remediation, and strengths and areas for improvement in remediation., Conclusions: The study concludes that identifying underperformers in the early stages of the medical curriculum and providing them with tailored remediation can enhance their performance in exams. Grade incentives in formative assessments, mind maps, quizzes, quick revisions, and assignments were beneficial remedial tools. Targeted remediation proved advantageous for students in improving their academic skills, exam preparation, time management, and attitudes towards the subject., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Research Committee and Institutional Ethics Committee at Srinivas Institute of Medical Sciences and Research Centre, Mangalore (Ref: SIMS & RC/IRC/UG/2023/001). The written informed consent forms were obtained from all participants. The work was conducted following the Declaration of Helsinki. All participants were provided with information on the study and gave consent. Consent for publication: Authors consent and abide by journal’s open access policy. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Cancer remains a leading cause of mortality, with non-small cell lung cancer (NSCLC) being a primary contributor to cancer-related deaths. Traditional treatment strategies such as chemotherapy, radiation, and hormone therapy often present challenges, including severe side effects, drug resistance, and toxicity. Recent advancements in nanotechnology aim to enhance the effectiveness of cancer therapies by targeting drugs selectively and specifically to tumor cells. Among these innovations, exosomes, or small extracellular vesicles (sEVs), have emerged as promising carriers for drug delivery due to their natural origin and ability to encapsulate both small molecules and biologics. This study explores the use of exosomes derived from camel milk in Hail, Saudi Arabia, as a vehicle for delivering curcumin (CUR), a polyphenol with known chemopreventive properties but limited bioavailability. Camel milk was processed to isolate exosomes through differential centrifugation, followed by characterization using dynamic light scattering, zeta potential measurements, and Western blot analysis to confirm exosomal markers. The encapsulation of CUR into camel milk-derived exosomes demonstrated a 20% loading efficiency as analyzed by UPLC. In vitro antiproliferative assays revealed that the exosomal formulation of CUR (ExoCUR) significantly enhanced cytotoxicity against drug-sensitive (A549) and taxol-resistant (A549TR) lung cancer cells compared to free CUR. Molecular docking studies and molecular dynamics simulations indicated that CUR has a strong binding affinity for the epidermal growth factor receptor (EGFR), comparable to the established drug gefitinib. Furthermore, CUR effectively downregulated EGFR and STAT3 expression in lung cancer cells, suggesting its potential to disrupt key signaling pathways involved in tumor progression. Our findings highlight the potential of camel milk-derived exosomes as an effective and biocompatible delivery system for CUR, offering a promising strategy to overcome the limitations of current cancer therapies and enhance the therapeutic efficacy of chemopreventive agents.

Background/Objectives : Lung cancer is one of the deadliest cancers, and drug resistance complicates its treatment. Mahanine (MH), an alkaloid from Murraya koenigii has been known for its anti-cancer properties. However, its effectiveness and mechanisms in treating non-small cell lung cancer (NSCLC) remain largely unexplored. The present study aimed to investigate MH's effect on drug-sensitive and drug-resistant NSCLC and its potential mechanism of action. Methods : We isolated MH from M. koenigii leaves and the purity (99%) was confirmed by HPLC, LC-MS and NMR. The antiproliferative activity of MH was determined using MTT and colony formation assays against drug-sensitive (A549 and H1299) and Taxol-resistant lung cancer cells (A549-TR). Western blot analysis was performed to determine MH's effects on various molecular targets. Anti-tumor activity of MH was determined against lung tumors developed in female NOD Scid mice injected with A549-Fluc bioluminescent cells (1.5 × 10 6 ) intrathoracically. Results : MH dose-dependently reduced the proliferation of all lung cancer cells (A549, H1299 and A549-TR), with IC50 values of 7.5, 5, and 10 µM, respectively. Mechanistically, MH arrested cell growth in the G0/G1 and G2/M phases of the cell cycle by inhibiting cyclin-dependent kinase 4/6 (CDK4/6) and cell division control 2 (CDC2) and induced apoptosis through the downregulation of B-cell leukemia/lymphoma 2 (BCL2) and B-cell lymphoma-extra large (BCL-XL). The apoptotic induction capacity of MH can also be attributed to its ability to inhibit pro-oncogenic markers, including mesenchymal-epithelial transition factor receptor (MET), phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), survivin, rat sarcoma viral oncogene (RAS), myelocytomatosis oncogene (cMYC), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) levels. In vivo, MH (25 mg/kg b. wt.) significantly ( p < 0.001) inhibited the growth of A549 lung cancer orthotopic xenografts in NOD Scid mice by 70%. Conclusions : Our study provides new mechanistic insights into MH's therapeutic potential against NSCLC.

Background: Hypothyroidism is known to affect a wide range of physiological systems, including menstrual function, in women of reproductive age. This study aims to comprehensively analyze the association between hypothyroidism and menstrual irregularities in women attending a tertiary care center., Methods: The study included 120 women aged 18-45 who presented with menstrual abnormalities. Convenience sampling was used to select participants from the outpatient department of obstetrics and gynecology. Thyroid function tests were conducted in the hospital's biochemistry laboratory, including assessments of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid peroxidase antibodies (TPOAb). The study aimed to determine the prevalence of hypothyroidism and its association with various menstrual irregularities, such as oligomenorrhea, polymenorrhea, menorrhagia, and amenorrhea. Data analysis was performed using SPSS software, applying descriptive statistics, Pearson correlation for continuous variables, and Chi-square tests for categorical variables. A significance level of p<0.05 was set for the analyses., Results: The mean age of the participants was 33.1 years (SD ± 7.2). The distribution of menstrual irregularities was 60 (50%) oligomenorrhea, 24 (20%) polymenorrhea, 24 (20%) menorrhagia, and 12 (10%) amenorrhea. Elevated TSH levels (>4.0 mIU/L) were observed in 42 (35%) of the participants, low FT4 levels (<0.8 ng/dL) in 18 (15%), low FT3 levels (<2.5 pg/mL) in 12 (10%), and elevated TPOAb levels (>55 IU/mL) in 24 (20%). A significant association was found between elevated TSH levels and oligomenorrhea (66 (55%), p<0.05) and between reduced FT4 levels and menorrhagia (78 (65%), p<0.05). Additionally, elevated TPOAb levels were significantly associated with amenorrhea (60 (50%), p<0.05). The correlation analysis showed a moderately positive correlation between TSH levels and the severity of menstrual irregularities (r=0.35, p<0.01). Subclinical hypothyroidism was detected in 25% of the participants, while 15% had clinical hypothyroidism., Conclusion: This study underscores a notable link between hypothyroidism and menstrual irregularities in women of reproductive age. The results highlight the necessity of routine thyroid function screenings for women experiencing menstrual abnormalities, facilitating precise diagnosis and suitable treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Kakatiya Institute of Ethical Committee issued approval KMC/Phy/KIEC/2021-8. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, P et al.)

Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition (DHC), which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies. Despite significant progress in reducing mortality rates from cardiovascular diseases (CVDs), heart failure remains a major cause of increased morbidity among diabetic patients. These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components, and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment. While a variety of conventional diagnostic and therapeutic strategies are available, DHC continues to present a significant challenge. Point-of-care diagnostics, supported by nanobiosensing techniques, offer a promising alternative for these complex scenarios. Although conventional medications have been widely used in DHC patients, they raise several concerns regarding various physiological aspects. Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC, offering a promising approach to deliver drugs beyond the limitations of traditional therapies. This article aims to explore the potential connections between autophagy, mitophagy and DHC, while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways., Competing Interests: The authors declare that they have no competing/conflicting interests., (© 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V.)

As one of the leading causes of global mortality and morbidity, various neurological diseases cause social and economic burdens. Despite significant advances in the treatment of neurological diseases, establishing a proper disease model, especially for degenerative and infectious diseases, remains a major challenging issue. For long, mice were the model of choice but suffered from serious drawbacks of differences in anatomical and functional aspects of the nervous system. Furthermore, the collection of post-mortem brain tissues limits their usage in cultured cell lines. Overcoming such limitations has prompted the usage of stem cells derived from the peripheral nervous system, such as the cells of the olfactory mucosa as a preferred choice. These cells can be easily cultured in vitro and retain the receptors of neuronal cells life-long. Such cells have various advantages over embryonic or induced stem cells, including homology, and ease of culture and can be conveniently obtained from diseased individuals through either biopsies or exfoliation. They have continuously helped in understanding the genetic and developmental mechanisms of degenerative diseases like Alzheimer's and Parkinson's disease. Moreover, the mode of infection of various viruses that can lead to post-viral olfactory dysfunction, such as the Zika virus can be monitored through these cells in vitro and their therapeutic development can be fastened., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

This study introduces a biosensor based on liquid crystals (LC) designed to detect the Aβ-42 biomarker, commonly associated with Alzheimer's disease. The sensor utilizes LC droplets created using a PEI/Tween-20 surfactant mixture, arranged radially in an aqueous solution. These droplets are coated with the Aβ1-16 antibody, enabling the detection of the Aβ1-42 biomarker. The key advantage of this biosensor lies in its ability to directly translate the antigen-antibody interaction into a change in the molecular orientation of the LC droplets, simplifying the detection process by removing additional procedural steps. Specifically, this immunoassay induces a transformation in the nematic droplets orientation from radial to bipolar upon successful antigen binding. When only the Aβ1-16 antibody coated the LC droplets, no change in orientation was detected, confirming the reaction's specificity. The orientation shift in the LC droplets indicates the formation of an immunocomplex between the Aβ1-16 antibody and the Aβ1-42 antigen. The LC droplet immunoassay effectively detected Aβ1-42 antigen concentrations ranging from 45 to 112.5 μM, with the Aβ1-16 antibody immobilized on the droplets at a concentration of 1 μg mL -1 . These findings suggest that the LC microdroplets' orientational behavior can be harnessed to develop a biosensor for the in vivo detection of various proteins or pathogens in a PBS aqueous medium. Owing to its label-free nature and distinct optical signaling, this LC droplet-based immunoassay holds promise for further development into a cost-effective, portable diagnostic tool., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Ethnopharmacological Relevance: Mahanine (MH), a naturally occurring carbazole alkaloid, isolated from Ayurvedic medicinal plant Murraya koenigii (L.) Spreng, has been shown to have various pharmacological properties, including its inhibitory activity against different breast cancers (BC) subtypes., Aim of the Study: While MH triggers apoptosis in BC cells regardless of subtype, the specific mechanism of MH action is not fully understood. In this study, we show the effect of MH in preventing BC progression by inducing apoptosis in relation to estrogen receptor-α (ERα) and cell cycle regulatory proteins., Materials and Methods: To assess the pharmacological activity in various in vitro and in vivo tests, isolated and pure MH was used. To conclude the study, cutting edged molecular biology techniques including Western blot analysis, enzyme-linked immunosorbent assay (ELISA), molecular simulation study, and other related software analysis were employed., Results: MH demonstrated dose dependent cell viability against drug sensitive (MCF-7 and MDA-MB-231) and paclitaxel resistant (MCF-7TR and MDA-MB-231TR) BC cells. MH also exhibited synergistic activity with tamoxifen (TAM) against estrogen receptor positive (ER+) BC cells by inhibiting ERα expression in MCF-7 cells and N-Methyl-N-nitrosourea (MNU)-induced mammary tumor in a dose-dependent manner while having no effect on vinculin expression. In addition, MH inhibited cell cycle regulatory genes namely CDK1/CDK4/CDK6/CDC25A and neo-angiogenesis through downregulation of CD31/PECAMs in MCF-7, MDA-MB-231 cells and mammary tumors from MNU-induced rats. MH therapy has been shown to be significantly able to lower the serum leptin level and to be beneficial against the initiation of tumor development in SD rats for up to 12 weeks. Molecular modeling study revealed that MH has antagonized the effectiveness of several types of estrogen those bind to the ERα and has comparable binding efficacy to TAM., Conclusion: Overall, the current investigation showed the ability of MH to modify cell cycle genes especially CDK4 and CDK6 might be responsible for its anticancer activity against different breast cancer subtypes. Additionally, this study will aid in advancing MH translational research to the clinical trial stage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Febrile seizures, convulsive episodes in young children during febrile illnesses, are a significant concern due to their potential for recurrence and associated uncertainties. This study investigated the causes and risks associated with recurrent febrile seizures and the critical role of electroencephalogram (EEG) in their accurate diagnosis., Methods: Following Institutional Review Board approval and going through the consenting process with parents, this study gathered the clinical features and EEG recordings of children admitted with febrile seizures in the Department of Pediatrics, Mahatma Gandhi Memorial Hospital, Kakatiya Medical College, Warangal, Telangana, India. Descriptive statistics, including mean, standard deviation (SD), frequencies, and percentages, were computed to understand the data comprehensively. The Chi-Square test was employed to analyze the association between variables, with a significance level of 0.05, ensuring reliable and trustworthy findings., Results: Out of 42 children studied, 28 (66.67%) presented with simple febrile seizures, with the mean time of occurrence of seizures from the onset of fever being 7.85 hours. Abnormal EEG was seen in 50% of children with complex febrile seizures and 16% with simple febrile seizures. Generalized epileptiform discharges were the most common epileptic activity observed. Low sodium levels had a significant relationship with febrile seizures in the analysis., Conclusions: This study emphasizes the importance of EEG in diagnosing febrile seizures, particularly in complex cases. Our findings suggest that low sodium levels may be a significant risk factor for febrile seizures. Further research is necessary to identify other preventable risk factors to reduce the burden of the medical condition., Competing Interests: None., (© 2023 Kuruva, Kompally, Bukkapatnam, Gudi, Kandimalla, Licensee HBKU Press.)

Multiple sclerosis (MS) is a chronic and degrading autoimmune disorder mainly targeting the central nervous system, leading to progressive neurodegeneration, demyelination, and axonal damage. Current treatment options for MS are limited in efficacy, generally linked to adverse side effects, and do not offer a cure. Stem cell therapies have emerged as a promising therapeutic strategy for MS, potentially promoting remyelination, exerting immunomodulatory effects and protecting against neurodegeneration. Therefore, this review article focussed on the potential of nano-engineering in stem cells as a therapeutic approach for MS, focusing on the synergistic effects of combining stem cell biology with nanotechnology to stimulate the proliferation of oligodendrocytes (OLs) from neural stem cells and OL precursor cells, by manipulating neural signalling pathways-PDGF, BMP, Wnt, Notch and their essential genes such as Sox, bHLH, Nkx. Here we discuss the pathophysiology of MS, the use of various types of stem cells in MS treatment and their mechanisms of action. In the context of nanotechnology, we present an overview of its applications in the medical and research field and discuss different methods and materials used to nano-engineer stem cells, including surface modification, biomaterials and scaffolds, and nanoparticle-based delivery systems. We further elaborate on nano-engineered stem cell techniques, such as nano script, nano-exosome hybrid, nano-topography and their potentials in MS. The article also highlights enhanced homing, engraftment, and survival of nano-engineered stem cells, targeted and controlled release of therapeutic agents, and immunomodulatory and tissue repair effects with their challenges and limitations. This visual illustration depicts the process of utilizing nano-engineering in stem cells and exosomes for the purpose of delivering more accurate and improved treatments for Multiple Sclerosis (MS). This approach targets specifically the creation of oligodendrocytes, the breakdown of which is the primary pathological factor in MS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Bacterial infections and persistent inflammation can impede the intrinsic healing process of wounds. To combat this issue, researchers have delved into the potential use of carbon dots (CDs) in the regulation of inflammation and counteract infections. These CDs were synthesized using a microwave-assisted hydrothermal process and have demonstrated outstanding antibacterial and antibiofilm properties against Gram-positive and Gram-negative bacteria. Additionally, CDs displayed biocompatibility at therapeutic concentrations and the ability to specifically target mitochondria. CD treatment effectively nullified lipopolysaccharide-triggered reactive oxygen species production by macrophages, while simultaneously promoting macrophage polarization toward an anti-inflammatory phenotype (M2), leading to a reduction in inflammation and an acceleration in wound healing. In vitro scratch assays also revealed that CDs facilitated the tissue-repairing process by stimulating epithelial cell migration during reepithelialization. In vivo studies using CDs topically applied to lipopolysaccharide (LPS)-stimulated wounds in C57/BL6 mice demonstrated significant improvements in wound healing due to enhanced fibroblast proliferation, angiogenesis, and collagen deposition. Crucially, histological investigations showed no indications of systemic toxicity in vital organs. Collectively, the application of CDs has shown immense potential in speeding up the wound-healing process by regulating inflammation, preventing bacterial infections, and promoting tissue repair. These results suggest that further clinical translation of CDs should be considered.

Diabetic nephropathy (DN) is a serious microvascular consequence of diabetes mellitus (DM), posing an encumbrance to public health worldwide. Control over the onset and progress of DN depend heavily on early detection and effective treatment. DN is a major contributor to end-stage renal disease, and a complete cure is yet to be achieved with currently available options. Though some therapeutic molecules have exhibited promise in treating DN complications, their poor solubility profile, low bioavailability, poor permeation, high therapeutic dose and associated toxicity, and low patient compliance apprehend their clinical usefulness. Recent research has indicated nano-systems as potential theranostic platforms displaying futuristic promise in the diagnosis and treatment of DN. Early and accurate diagnosis, site-specific delivery and retention by virtue of ligand conjugation, and improved pharmacokinetic profile are amongst the major advantages of nano-platforms, defining their superiority. Thus, the emergence of nanoparticles has offered fresh approaches to the possible diagnostic and therapeutic strategies regarding DN. The present review corroborates an updated overview of different types of nanocarriers regarding potential approaches for the diagnosis and therapy of DN., Competing Interests: Author LC is employed by the company BioAnalytical Lab, Meso Scale Discovery. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paul, Chacko, Dua, Chakraborty, Paul, Phulchand, Jha, Jha, Kandimalla and Dewanjee.)

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Current therapeutic strategies for PD are limited and mainly involve symptomatic relief, with no available treatment for the underlying causes of the disease. Therefore, there is a need for new therapeutic approaches that target the underlying pathophysiological mechanisms of PD. Calcium homeostasis is an essential process for maintaining proper cellular function and survival, including neuronal cells. Calcium dysregulation is also observed in various organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes, resulting in organelle dysfunction and impaired inter-organelle communication. The ER, as the primary calcium reservoir, is responsible for folding proteins and maintaining calcium homeostasis, and its dysregulation can lead to protein misfolding and neurodegeneration. The crosstalk between ER and mitochondrial calcium signaling is disrupted in PD, leading to neuronal dysfunction and death. In addition, a lethal network of calcium cytotoxicity utilizes mitochondria, ER and lysosome to destroy neurons. This review article focused on the complex role of calcium dysregulation and its role in aggravating functioning of organelles in PD so as to provide new insight into therapeutic strategies for treating this disease. Targeting dysfunctional organelles, such as the ER and mitochondria and lysosomes and whole network of calcium dyshomeostasis can restore proper calcium homeostasis and improve neuronal function. Additionally targeting calcium dyshomeostasis that arises from miscommunication between several organelles can be targeted so that therapeutic effects of calcium are realised in whole cellular territory., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Huntington's disease (HD) is a complex progressive neurodegenerative disorder affected by genetic, environmental, and metabolic factors contributing to its pathogenesis. Gut dysbiosis is termed as the alterations of intestinal microbial profile. Emerging research has highlighted the pivotal role of gut dysbiosis in HD, focusing on the gut-brain axis as a novel research parameter in science. This review article provides a comprehensive overview of gut microbiota dysbiosis and its relationship with HD and its pathogenesis along with the future challenges and opportunities. The focuses on the essential mechanisms which link gut dysbiosis to HD pathophysiology including neuroinflammation, immune system dysregulation, altered metabolites composition, and neurotransmitter imbalances. We also explored the impacts of gut dysbiosis on HD onset, severity, and symptoms such as cognitive decline, motor dysfunction, and psychiatric symptoms. Furthermore, we highlight recent advances in therapeutics including microbiota-based therapeutic approaches, including dietary interventions, prebiotics, probiotics, fecal microbiota transplantation, and combination therapies with conventional HD treatments and their applications in managing HD. The future challenges are also highlighted as the heterogeneity of gut microbiota, interindividual variability, establishing causality between gut dysbiosis and HD, identifying optimal therapeutic targets and strategies, and ensuring the long-term safety and efficacy of microbiota-based interventions. This review provides a better understanding of the potential role of gut microbiota in HD pathogenesis and guides the development of novel therapeutic approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no known cure, which has prompted the exploration of novel therapeutic approaches. The clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) tool has generated significant interest for its potential in AD therapeutics by correcting faulty genes. Our report comprehensively reviews emerging applications for CRISPR-Cas9 in developing in vitro and in vivo models for AD research and therapeutics. We further assess its ability to identify and validate genetic markers and potential therapeutic targets for AD. Moreover, we review the current challenges and delivery strategies for the in vivo application of CRISPR-Cas9 in AD therapeutics., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

An enveloped double-stranded DNA monkeypox virus (MPXV) is a causative agent of the zoonotic viral disease, human monkeypox (HMPX). MPXV belongs to the genus Orthopoxviridae, a family of notorious smallpox viruses, and so it shares similar clinical pathophysiological features. The recent multicountry HMPX outbreak (May 2022 onwards) is recognized as an emerging global public health emergency by the World Health Organization, shunting its endemic status as opined over the past few decades. Re-emergence of HMPX raises concern to reassess the present clinical strategy and therapeutics as its outbreak evolves further. Keeping a check on these developments, here we provide insights into the HMPX epidemiology, pathophysiology, and clinical representation. Weighing on its early prevention, we reviewed the strategies that are being enrolled for HMPX diagnosis. In the line of expanded MPXV prevalence, we further reviewed its clinical management and the diverse employed preventive/therapeutic strategies, including vaccines (JYNNEOS, ACAM2000, VIGIV) and antiviral drugs/inhibitors (Tecovirimat, Cidofovir, Brincidofovir). Taken together, with a revised perspective of HMPX re-emergence, the present report summarizes new knowledge on its prevalence, pathology, and prevention strategies.

Cancer has recently surpassed heart disease as the leading cause of deaths worldwide for the age group 45-65 and has been the primary focus for biomedical researchers. Presently, the drugs involved in the first-line cancer therapy are raising concerns due to high toxicity and lack of selectivity to cancer cells. There has been a significant increase in research with innovative nano formulations to entrap the therapeutic payload to enhance efficacy and eliminate or minimize toxic effects. Lipid-based carriers stand out due to their unique structural properties and biocompatible nature. The two main leaders of lipid-based drug carriers: long known liposomes and comparatively new exosomes have been well-researched. The similarity between the two lipid-based carriers is the vesicular structure with the core's capability to carry the payload. While liposomes utilize chemically derived and altered phospholipid components, the exosomes are naturally occurring vesicles with inherent lipids, proteins, and nucleic acids. More recently, researchers have focused on developing hybrid exosomes by fusing liposomes and exosomes. Combining these two types of vesicles may offer some advantages such as high drug loading, targeted cellular uptake, biocompatibility, controlled release, stability in harsh conditions and low immunogenicity., Competing Interests: Declaration of competing interest Dr. Ramesh C. Gupta holds positions both at the University of Louisville and 3P Biotechnologies, Inc. The authors have filed an international patent application (PCT) based on part of the results reported in this paper. All other authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

It is known that alcoholic beverages alter the human gut microbiome. This study focused on the potential impact of non-ethanolic ingredients in whisky on the gut bacteriome. A pilot study was carried out on 15 whisky drinkers, 5 rice beer drinkers, and 9 non-drinkers to determine the effect of alcoholic beverages on the host microbiome and metabolome. Additionally, a mouse model was used to assess the differential impact of three whisky brands (each with an equal ethanol concentration). The results indicate that the non-ethanolic components have an impact on the gut microbiome, as well as on the metabolites in blood and feces. The amount of Prevotella copri , a typical core Indian gut bacterium, decreased in both the human and mouse groups of whisky type 1, but an increase in abundance of Helicobacteriaceae ( p = 0.01) was noticed in both groups. Additionally, the alcohol-treated cohorts had lower levels of short-chain fatty acids (SCFAs), specifically butyric acid, and higher amounts of lipids and stress marker IL1-ß than the untreated groups ( p = 0.04-0.01). Furthermore, two compounds, ethanal/acetaldehyde (found in all the whisky samples) and arabitol (unique to whisky type 1), were tested in the mice. Similar to the human subjects, the whisky type 1 treated mouse cohort and the arabitol-treated group showed decreased levels of Prevotella copri ( p = 0.01) in their gut. The results showed that non-ethanolic compounds have a significant impact on host gut bacterial diversity and metabolite composition, which has a further vital impact on host health. Our work further emphasizes the need to study the impact of non-ethanolic ingredients of alcoholic beverages on host health.

Diabetes mellitus (DM) and cardiovascular complications are two unmet medical emergencies that can occur together. The rising incidence of heart failure in diabetic populations, in addition to apparent coronary heart disease, ischemia, and hypertension-related complications, has created a more challenging situation. Diabetes, as a predominant cardio-renal metabolic syndrome, is related to severe vascular risk factors, and it underlies various complex pathophysiological pathways at the metabolic and molecular level that progress and converge toward the development of diabetic cardiomyopathy (DCM). DCM involves several downstream cascades that cause structural and functional alterations of the diabetic heart, such as diastolic dysfunction progressing into systolic dysfunction, cardiomyocyte hypertrophy, myocardial fibrosis, and subsequent heart failure over time. The effects of glucagon-like peptide-1 (GLP-1) analogues and sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular (CV) outcomes in diabetes have shown promising results, including improved contractile bioenergetics and significant cardiovascular benefits. The purpose of this article is to highlight the various pathophysiological, metabolic, and molecular pathways that contribute to the development of DCM and its significant effects on cardiac morphology and functioning. Additionally, this article will discuss the potential therapies that may be available in the future.

The devastating complications of coronavirus disease 2019 (COVID-19) result from an individual's dysfunctional immune response following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events ultimately leading to COVID-19. The current study identifies eighty immune system dysfunction-enabling toxic stressors and behaviors (hereafter called modifiable contributing factors (CFs)) that also link directly to COVID-19. Each CF is assigned to one of the five categories in the CF taxonomy shown in Section 3.3.: Lifestyle (e.g., diet, substance abuse); Iatrogenic (e.g., drugs, surgery); Biotoxins (e.g., micro-organisms, mycotoxins); Occupational/Environmental (e.g., heavy metals, pesticides); Psychosocial/Socioeconomic (e.g., chronic stress, lower education). The current study shows how each modifiable factor contributes to decreased immune system capability, increased inflammation and coagulation, and increased neural damage and neurodegeneration. It is unclear how real progress can be made in combatting COVID-19 and other similar diseases caused by viral variants without addressing and eliminating these modifiable CFs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) has been the most extensively studied neurological disorders that affects millions of individuals globally and is associated with misfolding of proteins in the brain. Amyloid-β and tau are predominantly involved in the pathogenesis of AD. Therapeutic interventions and nanotechnological advancements are useful only in managing the AD symptoms and the cure for this disease remains elusive. Exosomes, originating from most cell and tissue types are regarded as a double-edged sword, considering their roles in the progression and treatment of AD. Exosomes can be manipulated as drug delivery vehicles for a wide range of therapeutic cargos-both small molecules and macromolecules. Herein, we review the roles of exosomes in the pathology, diagnosis, and treatment of AD and highlight their application as a drug carrier to the brain for AD treatment., Competing Interests: Declaration of Competing Interest We declare that there are no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Increasing evidence suggests that abnormal cerebral glucose metabolism is largely present in Alzheimer's disease (AD). The brain utilizes glucose as its main energy source and a decline in its metabolism directly reflects on brain function. Weighing on recent evidence, here we systematically assessed the aberrant glucose metabolism associated with amyloid beta and phosphorylated tau accumulation in AD brain. Interlink between insulin signaling and AD highlighted the involvement of the IRS/PI3K/Akt/AMPK signaling, and GLUTs in the disease progression. While shedding light on the mitochondrial dysfunction in the defective glucose metabolism, we further assessed functional consequences of AGEs (advanced glycation end products) accumulation, polyol activation, and other contributing factors including terminal respiration, ROS (reactive oxygen species), mitochondrial permeability, PINK1/parkin defects, lysosome-mitochondrial crosstalk, and autophagy/mitophagy. Combined with the classic plaque and tangle pathologies, glucose hypometabolism with acquired insulin resistance and mitochondrial dysfunction potentiate these factors to exacerbate AD pathology. To this end, we further reviewed AD and DM (diabetes mellitus) crosstalk in disease progression. Taken together, the present work discusses the emerging role of altered glucose metabolism, contributing impact of insulin signaling, and mitochondrial dysfunction in the defective cerebral glucose utilization in AD., (Copyright © 2022 Elsevier Inc. All rights reserved.)