Correction: Enantioselective total synthesis of atisane diterpenoids: (+)-sapinsigin H, (+)-agallochaol C, and (+)-16α, 17-dihydroxy-atisan-3-one.

Correction for 'Enantioselective total synthesis of atisane diterpenoids: (+)-sapinsigin H, (+)-agallochaol C, and (+)-16α, 17-dihydroxy-atisan-3-one' by Dattatraya H. Dethe et al., Chem. Commun., 2024, 60, 7866-7869, https://doi.org/10.1039/D4CC01982B.

Nanoparticles encapsulated in Abelmoschus esculentus polysaccharide-based pellets as colon targeting approach.

AIM(S): This article explores the application of mesalazine-loaded nanoparticles (MLZ-NPs) encapsulated in Abelmoschus esculentus plant polysaccharide-based pellets (MLZ-NPs-Pellets) for ulcerative colitis. METHODS: MLZ-NPs were prepared and evaluated for diameter, PDI, and entrapment efficiency. In-vitro efficacy study was conducted on Caco-2 cells. MLZ-NPs were encapsulated in polysaccharides to form MLZ-NPs-Pellets and characterised for efficacy in animals and targeting efficiency in human volunteers. RESULTS: Optimised batch of MLZ-NPs were characterised for diameter, PDI, zeta potential and entrapment efficiency which was found to be 145.42 ± 6.75 nm, 0.214 ± 0.049, -31.63 mV and 77.65 ± 2.33(%w/w) respectively. ROS, superoxide and NF-kß were well controlled in Caco-2 cells when treated with MLZ-NPs. In-vivo data revealed that some parameters (body weight, colon length, lipid peroxidase, and glutathione) recovered significantly in the DSS-induced mice model treated with oral MLZ-NPs-Pellets. Gamma scintigraphy revealed that the formulation can effectively target the colon within 600 min. CONCLUSION: MLZ-NPs-Pellets can be effectively used for microbial-triggered colon targeting approach in treating ulcerative colitis.

Unveiling the Applications of Phytoconstituents in Neuropathic Pain.

BACKGROUND: Neuropathic pain is a complex chronic condition resulting from the damage or dysfunction of the nervous system. Conventional therapies offer limited success and often come with various adverse effects. Therefore, the exploration of alternative therapies, such as phytoconstituents, may be of substantial interest for their potential to alleviate neuropathic pain. OBJECTIVES: This review systematically examines the diverse roles and mechanisms of various phytoconstituents in modulating neuropathic pain. In this study, a comprehensive analysis of phytoconstituents in neuropathic pain is carried out to understand their mechanism in preventing the disease. METHOD: The current search is done in the databases of Google Scholar, PubMed Central, ScienceDirect, and Scopus using the keywords: neuropathic pain, phytoconstituents as analgesics, physiological effects of medicinal plants, and natural products, to find the most relevant articles of the last 10 years. RESULT: Out of 125 articles, 112 were included in this study, which revealed that several phytoconstituents inhibit several biomarkers responsible for neuropathic pain. Moreover, this review highlights the underlying molecular pathways and targets through which these bioactive compounds exert their therapeutic effects, emphasizing their potential as novel pharmacological agents. CONCLUSION: This study concludes that phytoconstituents may possess potential applications in managing neuropathic pain and could be effectively used as an alternative approach to mitigate the condition with enhanced risk of safety and tolerability.

Clopidogrel resistance and its effect on clinical outcomes in acute coronary syndrome.

AIM: The genetic polymorphism of CYP2C19 influences clopidogrel metabolism and resistance. Aim was to assess the association between CYP2C19 loss of function variation, clopidogrel resistance based on platelet reactivity units and clinical outcomes. METHODS: A total of 668 patients of Acute Coronary Sundrome (ACS) who underwent Percutaneous Coronary Intervention (PCI) were subjected to genetic screening and 143 patients undrewent platelet function test to study the association between drug metabolization and its effects based on platelet reactivity unit values. RESULTS: Clopidogrel resistance with CYP2C 19 loss of function variation was noted in 54.64% of patients. Clinical outcomes, such as target vessel revascularization, target lesion revascularization, in-stent restenosis, and stent thrombosis, were also studied. CONCLUSION: CYP2C19 loss of function variation is strongly associated with clopidogrel resistance and adverse clinical outcomes.

Enantioselective total synthesis of atisane diterpenoids: (+)-sapinsigin H, (+)-agallochaol C, and (+)-16α, 17-dihydroxy-atisan-3-one.

Enantioselective total synthesis of (+)-sapinsigin H, (+)-agallochaol C, and (+)-16α, 17-dihydroxy-atisan-3-one has been accomplished starting from enantiopure Wieland-Miescher ketone. Key features of the syntheses include a benzannulation step to construct the tricyclic core, an oxidative dearomatization step to generate the diene, and a Diels-Alder reaction with ethylene gas to establish the bicyclo[2.2.2]octane framework. Efficient late-stage functionalisation of the A-ring by aerobic oxidation and Baeyer-Villiger oxidation completed the atisane target molecules.

Head-to-head comparison of relevant cell sources of small extracellular vesicles for cardiac repair: Superiority of embryonic stem cells.

Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC-derived sEV (ESC-sEV) exhibited the best pro-angiogenic and anti-fibrotic effects in vitro. Then, we evaluated the functionality of the sEV with the most promising performances in vitro, in a murine model of MI-reperfusion injury (IRI) and analysed their RNA and protein compositions. In vivo, ESC-sEV provided the most favourable outcome after MI by reducing adverse cardiac remodelling through down-regulating fibrosis and increasing angiogenesis. Furthermore, transcriptomic, and proteomic characterizations of sEV derived from hTERT-MSC, ESC, and CPC revealed factors in ESC-sEV that potentially drove the observed functions. In conclusion, ESC-sEV holds great promise as a cell-free treatment for promoting cardiac repair following MI.

Dual-strain dynamics of COVID-19 variants in India: Modeling, analysis, and implications for pandemic control.

This study introduces a detailed compartmental model developed to understand the complex dynamics of COVID-19 transmission, focusing on the Delta and Omicron variants in India. The model tracks disease progression through different population compartments, considering factors like vaccination, time-dependent transmission, economic burden and COVID-19 death rates, loss of vaccine-induced immunity, and the transition of asymptomatic cases to recovery. The model is validated against established epidemiological knowledge and real-world data, emphasizing dynamic parameterization and accurate representation of immunity dynamics. The basic reproduction number for both variants is calculated, and sensitivity analysis for various parameters is conducted. Time-dependent parameters are estimated using the discrete inverse method. The study also explores the economic burden, impact of different types of masks, vaccine efficacy, and vaccine-induced immunity through numerical analysis.

Flap Closure in Neonatal Neural Tube Defects: Challenges in Flap Design and Lessons Learnt.

Background: Management of neural tube defects (NTDs) is challenging and the outcome is demanding. Aims: To analyze the outcomes in operated cases of NTDs closed using various types of flaps. Materials and Methods: The data between June 2017 and May 2023 were analyzed. The mode of presentation, timing of intervention, type of flap, neurological status after closure, status of the wound, presence of hydrocephalous, flap blackening, flap necrosis, features of sepsis, and the outcome were recorded and analyzed. Covered NTD; closure done using primary closure or 'Z' Plasty (everywhere); incomplete data; lost to follow-up; and not giving consent were excluded from the study. Results: Out of 92 cases, 35 were operated using the rhomboid flap, 33 using dufourmentel modification of limberg flap, and 24 using keystone island flap. The mean age at presentation was 4 days (range: 0-28 days). The mean duration of surgery after presentation was 2 days (range: 1-3 days). Mean operating time was 1.15 h (range: 0.45-3.15 h). A ventriculoperitoneal shunt was required in 62 cases at various stages. The preoperative and the postoperative power were nearly the same in all. Wound infection was seen in 2, 3, and 1 cases in each group. Blackening of the flap was seen in 3, 2, and 1 cases in three groups. Cerebrospinal fluid (CSF) leak was seen in 2, 2, and 0 cases. Wound dehiscence was present in one case in each group and sepsis was present in 2, 3, and 2, respectively. Conclusion: The management of open NTD requires adequate planning. CSF shunting and flap closure are often required.

Asymmetric Total Synthesis of (+)-Verrubenzospirolactone and (+)-Capillobenzopyranol.

The first asymmetric total synthesis of (+)-verrubenzospirolactone (1), a distinctive highly fused benzosesquiterpenoid, characterized by a pentacyclic skeletal structure, is realized through a concise 10-step synthetic pathway with an impressive 22.8% overall yield. Notable highlights of this synthetic endeavor include (i) the introduction of a Ru-catalyzed ortho C-H activation step, (ii) the application of Pd-catalyzed asymmetric allylic alkylation to establish a pivotal stereocenter at C-3 with an excellent enantiomeric excess, (iii) B-alkyl Suzuki-Miyaura coupling to construct a Diels-Alder precursor, and, ultimately, (iv) the successful deployment of an intramolecular Diels-Alder reaction to complete the synthesis of (+)-verrubenzospirolactone without erosion of the enantiomeric excess.

Therapeutic proteins: developments, progress, challenges, and future perspectives.

Proteins are considered magic molecules due to their enormous applications in the health sector. Over the past few decades, therapeutic proteins have emerged as a promising treatment option for various diseases, particularly cancer, cardiovascular disease, diabetes, and others. The formulation of protein-based therapies is a major area of research, however, a few factors still hinder the large-scale production of these therapeutic products, such as stability, heterogenicity, immunogenicity, high cost of production, etc. This review provides comprehensive information on various sources and production of therapeutic proteins. The review also summarizes the challenges currently faced by scientists while developing protein-based therapeutics, along with possible solutions. It can be concluded that these proteins can be used in combination with small molecular drugs to give synergistic benefits in the future.

Physical characterization and bioavailability assessment of 5-fluorouracil-based nanostructured lipid carrier (NLC): In vitro drug release, Hemolysis, and permeability modulation.

5-Fluorouracil (5-FU) is an anticancer agent belonging to BCS Class III that exhibits poor release characteristics and low retention in the biological system. The main objective of this investigation was to develop a drug delivery system, i.e., Nanostructure Lipid Carriers (NLCs) loaded with 5-FU to prolong its biological retention through 5-FU-loaded NLCs (5-FUNLC) were designed to manipulate physicochemical characteristics and assessment of in vitro and in vivo performance. The developed NLCs underwent comprehensive characterization, including assessments for particle size, zeta potential, morphological evaluation, and FT-IR spectroscopy. Additionally, specific evaluations were conducted for 5-FUNLCs, encompassing analyses for encapsulation efficiency of the drug, release characteristics in PBS at pH 6.8, and stability study. The lipophilic character of 5-FUNLC was confirmed through the measurement of the partition coefficient (log P). 5-FUNLCs were observed as spherical-shaped particles with a mean size of 300 ± 25 nm. The encapsulation efficiency was determined to be 89%, indicating effective drug loading within the NLCs. Furthermore, these NLCs exhibited a sustained release nature lasting up to 3-4 h, indicating their potential for controlled drug release over time. Lipid components were biocompatible with the 5-FU to determine thermal transition temperature and show good stability for 30 days. Additionally, an in vitro hemolysis study that confirmed the system did not cause any destruction to the RBCs during intravenous administration. The drug's gut permeability was assessed utilizing the optimized 5-FUNLC (F2) in comparison to 5-FU through the intestine or gut sac model (in the apical to basolateral direction, A → B). The permeability coefficient was measured as 4.91 × 10-5 cm/h with a significant difference. Additionally, the antioxidant potential of the NLCs was demonstrated through the DPPH method. The NLCs' performance was further assessed through in vivo pharmacokinetic studies on Wistar Rats, resulting in a 1.5-fold enhancement in their activity compared to free 5-FU. These NLCs offer improved drug solubility and sustained release, which collectively contribute to enhanced therapeutic outcomes and modulate bioavailability. The study concludes by highlighting the potential of 5-FUNLC as an innovative and efficient drug delivery system. The findings suggest that further preclinical investigations are warranted, indicating a promising avenue for the development of more effective and well-tolerated treatments for cancer.

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.

Nanoparticles toxicity: an overview of its mechanism and plausible mitigation strategies.

Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.

Prognostic role of PD-L1 expression in head and neck squamous cell carcinoma: An institutional experience from India.

BACKGROUND: Squamous cell carcinoma accounts for > 90% of Head and neck cancers and has a poor 5-year survival rate of only 50%. Immunosuppressive agents like PD-L1 inhibitors have been found to improve survival in many tumour types, including advanced/recurrent head and neck squamous cell carcinoma (HNSCC). The PD-L1 expression in this tumour can also predict clinical outcome. However, this fact still remains to be proven. AIM: The aim was to study the expression of PD-L1 in HNSCC, correlate with clinicopathological parameters and outcome. MATERIAL AND METHOD: This prospective study was conducted between March 2021 to June 2023 in department of Pathology of a tertiary care centre located in northern India. A total of 65 histologically confirmed cases of HNSCC were included. Expression of PD-L1 was determined by immunohistochemistry. The combined positive (CPS) and tumour proportion (TP) scores were calculated. The results were correlated with clinicopathological parameters and outcome using appropriate statistical tools. RESULTS: Considering CPS, 42 (64.6%) cases showed expression of PD-L1. A high score of ≥ 20% was seen in 10 cases (15.4%). PD-L1 expression did not correlate with any of the clinical parameters including age, gender, addiction, site, TNM stage and HPV status. Conventional HNSCC had significantly higher expression of PD-L1. The cases with positive PD-L1 expression had a higher mean survival and a lower mortality, but the difference was not statistically significant. CONCLUSION: PD-L1 expression is more likely to be seen in conventional HNSCC histomorphology. PD-L1 expression is a predictor of better prognosis in HNSCC.

Inner Ear Function Evaluation in Mobile Phone Users: A Cross-Sectional Study From a Tertiary Care Centre in North India.

Background India has approximately 1.02 billion mobile phone users. The electromagnetic radiations emitted by telecommunication systems are absorbed by the recipient's body, leading to changes in brain electrical activity, sensations of warmth or burning around the ear, and alterations in the blood-brain barrier. The inner ear, being the closest organ during mobile phone use, directly receives these electromagnetic radiations. This study aims to assess the inner ear function among mobile phone users, investigate the impact of mobile phones on the hearing thresholds of volunteers through pure-tone audiometry (PTA), and delve into the same using otoacoustic emissions (OAE). Methodology A cross-sectional study was conducted at a single center in North India from September 2020 to March 2021. The sample size of around 100 was determined using G Power software (G Power, Aichach, Germany), including volunteers aged 18-25, using mobile phones for over a year with normal hearing. Exclusions involved various ear-related histories or chronic systemic illnesses. Dominant and non-dominant ear groups were formed based on mobile phone usage. The study involved comprehensive ENT examinations, pure-tone audiometry, and otoacoustic emissions. We performed statistical analyses using SPSS version 22.0 (IBM Corp., Armonk, NY), which presented descriptive statistics and employed tests for group comparisons. Results Most participants were in the 21-23 age group (56%), with a mean age of 22.16 ± 1.77 years. There were 45 males and 55 females. The mean mobile phone usage was 6.6 ± 1.98 years, with varying daily durations. The dominant ear for mobile phone usage was predominantly the right ear (75 participants). Pure-tone audiometry results showed no statistically significant differences between dominant and non-dominant ears. Among the 24 participants with absent OAE, no significant association was found with mobile phone usage duration. Notably, the highest incidence of absent OAE occurred in the 120-180-minute usage category. Conclusion Mobile phones have seamlessly integrated into the lives of individuals, witnessing an exponential increase in users over time. The inner ear, situated in proximity to mobile phone usage, is of particular concern. While there is existing evidence indicating potential adverse effects of mobile phones on the inner ear, further long-term studies involving larger populations are essential to comprehensively evaluating the impact on inner ear function among mobile phone users.

Apple (Malus × domestica Borkh.) production and quality in response to anti-hail nets.

Anti-hail nets are the best way to mitigate the effects of hailstorms in the orchards. Apple trees covered with nets may exhibit a variety of vegetative and reproductive responses, inclusive of changes in tree vigour, cropping, sugar contents, and fruit colour. The present study was conducted to assess the effect of timing of installation and colour of anti-hail net on cropping and fruit quality in high-density apple orchard for two consecutive seasons (2021 and 2022). White and blue colour nets of size (9 m × 30 m) 80 GSM (square mesh with non-sliding threaded, leno weave, and < 30% shading factor) were installed at three different time intervals (15 days before estimated full bloom, at full bloom, and 15 days after full bloom) on apple cultivar 'Jeromine'. The installation at different time and colour of anti-hail nets significantly exhibit variability in cropping, fruit quality, and bio-chemical metrics. The significant highest cropping (fruit yield, productivity, and yield efficiency) and fruit biochemical parameters (total soluble solids) were recorded in T3C2 (15 days after full bloom + white colour anti-hail net) followed by T2C2 (installed at full bloom + white colour anti-hail net). Hence, white colour anti-hail nets installed 15 days after full bloom increased fruit production and improved quality in comparison to blue colour anti-hail net in apple under high-density plantations.

A review of botany, traditional applications, phytochemistry, pharmacological applications, and toxicology of Rubus ellipticus Smith fruits.

Rubus ellipticus Smith. (Family Rosaceae), often known as the yellow Himalayan raspberry (Yellow Hissar), is one of the most widely used edible fruits in Indian folk medicinal systems. The current review aims to identify the gap between research and existing applications of this fruit to help scientists explore the current trends and opportunities for future development. Fruits of R. ellipticus are the source of several classes of compounds. Fruits of R. ellipticus are also rich in nutrients such as carbohydrates, vitamins, and minerals. It has been shown to have significant medical value in a variety of studies, including as an anti-diabetic, nephroprotective, anti-inflammatory, analgesic, antipyretic, antitumor, wound healing, antifertility, oviposition deterrent, antibacterial, and antioxidant. Fruits of R. ellipticus have been the subject of several in vitro and in vivo investigations, all of which have corroborated their wide range of biological activities and demonstrated their potential for the identification of new therapeutic candidates and the development of innovative herbal food supplements. Additional mechanism-based pharmacological evaluation and clinical research should provide an adequate scientific basis for the traditional usage of R. ellipticus fruits, which is currently not sufficiently supported by the available research on its active components and molecular mechanisms.

A clustering-based method for estimating pennation angle from B-mode ultrasound images.

B-mode ultrasound (US) is often used to noninvasively measure skeletal muscle architecture, which contains human intent information. Extracted features from B-mode images can help improve closed-loop human-robotic interaction control when using rehabilitation/assistive devices. The traditional manual approach to inferring the muscle structural features from US images is laborious, time-consuming, and subjective among different investigators. This paper proposes a clustering-based detection method that can mimic a well-trained human expert in identifying fascicle and aponeurosis and, therefore, compute the pennation angle. The clustering-based architecture assumes that muscle fibers have tubular characteristics. It is robust for low-frequency image streams. We compared the proposed algorithm to two mature benchmark techniques: UltraTrack and ImageJ. The performance of the proposed approach showed higher accuracy in our dataset (frame frequency is 20 Hz), that is, similar to the human expert. The proposed method shows promising potential in automatic muscle fascicle orientation detection to facilitate implementations in biomechanics modeling, rehabilitation robot control design, and neuromuscular disease diagnosis with low-frequency data stream.