Quinolone scaffolds as potential drug candidates against infectious microbes: a review.

Prevalence of microbial infections and new rising pathogens are signified as causative agent for variety of serious and lethal health crisis in past years. Despite medical advances, bacterial and fungal infections continue to be a rising problem in the health care system. As more bacteria develop resistance to antibiotics used in therapy, and as more invasive microbial species develop resistance to conventional antimicrobial drugs. Relevant published publications from the last two decades, up to 2024, were systematically retrieved from the MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as quinolones, anti-infective, antibacterial, antimicrobial resistance and patents on quinolone derivatives. With an approach of considerable interest towards novel heterocyclic derivatives as novel anti-infective agents, researchers have explored these as essential tools in vistas of drug design and development. Among heterocycles, quinolones have been regarded extremely essential for the development of novel derivatives, even able to tackle the associated resistance issues. The quinolone scaffold with its bicyclic structure and specific functional groups such as the carbonyl and acidic groups, is indeed considered a valuable functionalities for further lead generation and optimization in drug discovery. Besides, the substitution at N-1, C-3 and C-7 positions also subjected to be having a significant role in anti-infective potential. In this article, we intend to highlight recent quinolone derivatives based on the SAR approach and anti-infective potential such as antibacterial, antifungal, antimalarial, antitubercular, antitrypanosomal and antiviral activities. Moreover, some recent patents granted on quinolone-containing derivatives as anti-infective agents have also been highlighted in tabular form. Due consideration of this, future research in this scaffold is expected to be useful for aspiring scientists to get pharmacologically significant leads.

Synergistic microwave and acidic deep eutectic solvent-based pretreatment of Theobroma cacao pod husk biomass for xylooligosaccharides production.

The bioconversion of lignocellulosic biomass into novel bioproducts is crucial for sustainable biorefineries, providing an integrated solution for circular economy objectives. The current study investigated a novel microwave-assisted acidic deep eutectic solvent (DES) pretreatment of waste cocoa pod husk (CPH) biomass to extract xylooligosaccharides (XOS). The sequential DES (choline chloride/citric acid, molar ratio 1:1) and microwave (450W) pretreatment of CPH biomass was effective in 67.3% xylan removal with a 52% XOS yield from total xylan. Among different XOS of varying degrees of polymerization, a higher xylobiose content corresponding to 69.3% of the total XOS (68.22 mg/g CPH) from liquid fraction was observed. Enzymatic hydrolysis of residual xylan from pretreated CPH biomass with low commercial xylanase (10 IU/g) concentration yielded 24.2% XOS. The MW-ChCl/citric acid synergistic pretreatment approach holds great promise for developing a cost-effective and environmentally friendly method contributing to the sustainable production of XOS from agricultural waste streams.

A systematic review of EEG based automated schizophrenia classification through machine learning and deep learning.

The electroencephalogram (EEG) serves as an essential tool in exploring brain activity and holds particular importance in the field of mental health research. This review paper examines the application of artificial intelligence (AI), encompassing machine learning (ML) and deep learning (DL), for classifying schizophrenia (SCZ) through EEG. It includes a thorough literature review that addresses the difficulties, methodologies, and discoveries in this field. ML approaches utilize conventional models like Support Vector Machines and Decision Trees, which are interpretable and effective with smaller data sets. In contrast, DL techniques, which use neural networks such as convolutional neural networks (CNNs) and long short-term memory networks (LSTMs), are more adaptable to intricate EEG patterns but require significant data and computational power. Both ML and DL face challenges concerning data quality and ethical issues. This paper underscores the importance of integrating various techniques to enhance schizophrenia diagnosis and highlights AI's potential role in this process. It also acknowledges the necessity for collaborative and ethically informed approaches in the automated classification of SCZ using AI.

A Profound Insight into the Structure-activity Relationship of Ubiquitous Scaffold Piperazine: An Explicative Review.

Despite extensive research in the field of drug discovery and development, still there is a need to develop novel molecular entities. Literature reveals a substantial heterocyclic nucleus named, piperazine, which shows an immense therapeutic voyage. For several decades, molecules having the piperazine nucleus have entered the market as a drug exhibiting biological potential. It was known to possess antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardioprotective, and anti-inflammatory activity with a specific basis for structural activity relationship. Thus, it is regarded as a key structural feature in most of the already available therapeutic drugs in the market. Reports also suggest that the extensive utilization of these currently available drugs having a piperazine nucleus shows increasing tolerance significantly day by day. In addition to this, various other factors like solubility, low bioavailability, cost-effectiveness, and imbalance between pharmacokinetics and pharmacodynamics profile limit their utilization. Focusing on that issues, various structural modification studies were performed on the piperazine moiety to develop new derivatives/analogs to overcome the problems associated with available marketed drugs. Thus, this review article aims to gain insight into the number of structural modifications at the N-1 and N-4 positions of the piperazine scaffold. This SAR approach may prove to be the best way to overcome the above-discussed drawbacks and lead to the design of drug molecules with better efficacy and affinity. Hence, there is an urgent need to focus on the structural features of this scaffold which paves further work for deeper exploration and may help medicinal chemists as well as pharmaceutical industries.

PAS Dimerization at the Nexus of the Mammalian Circadian Clock.

Circadian rhythms are genetically encoded molecular clocks for internal biological timekeeping. Organisms from single-cell bacteria to humans use these clocks to adapt to the external environment and synchronize their physiology and behavior to solar light/dark cycles. Although the proteins that constitute the molecular 'cogs' and give rise to circadian rhythms are now known, we still lack a detailed understanding of how these proteins interact to generate and sustain the ∼24-hour circadian clock. Structural studies have helped to expand the architecture of clock proteins and have revealed the abundance of the only well-defined structured regions in the mammalian clock called Per-ARNT-Sim (PAS) domains. PAS domains are modular, evolutionarily conserved sensory and signaling domains that typically mediate protein-protein interactions. In the mammalian circadian clock, PAS domains modulate homo and heterodimerization of several core clock proteins that assemble into transcription factors or repressors. This review will focus on the functional importance of the PAS domains in the circadian clock from a biophysical and biochemical standpoint and describe their roles in clock protein interactions and circadian timekeeping.

Comparative evaluation of milk proteins and oil-seed-cake-derived proteins extracted by chemical and biological methods for obesity management.

BACKGROUND: In light of the exponential rise in global population, there is a critical requirement to reduce food waste on a global scale. According to studies, agricultural wastes such as oil-seed cakes offer great nutritional value. Acid precipitation (A) and alkaline extraction methods (traditional methods) were used to extract protein from oil-seed cakes; however, both procedures are linked to decreased protein quality and quantity, which prompted the development of a novel strategy known as the biological/microbial/probiotic (B) method. Therefore, the present study aimed to highlight the optimal way of protein extraction from oil-seed cakes and the effect of extraction methods on protein efficacy against obesity. The outcomes were also compared with milk proteins. RESULTS: In vitro study provided evidence that proteins from both sources (plant and milk) suppressed adipogenesis and stimulated adipolysis in 3T3L-1 cells. For the in vivo study, mice were fed with different protein extracts: soya protein preparation (SPP), ground protein preparation (GPP), whey protein (WP) and casein protein (CP) containing 40% of their calories as fat. Body weight decreased significantly in all the rats except CP-fed rats. Body mass index, atherogenic index, plasma triglyceride and very-low-density lipoprotein cholesterol level decreased significantly in all the groups in comparison to the model group (high-fat-diet group), but the decrease was more pronounced in plant proteins than milk proteins. In hepatocytes, the expression of fasting-induced adipose factor, carnitine palmitoyltransferase I and peroxisome proliferator-activated receptor α genes was increased significantly in SPP-fed groups. Adiponectin gene expression was upregulated significantly in visceral fat tissue in groups fed SPP-B, GPP-A and CP, whereas leptin gene was downregulated significantly in all groups except SPP-A. CONCLUSION: This study demonstrates that SPP-B showed the most effective anti-obesity property, followed by WP. Additionally, we found that the biological precipitation approach produced better outcomes for plant proteins isolated from oil-seed cakes than the acid precipitation method. © 2023 Society of Chemical Industry.

Women's awareness of perinatal mental health conditions and the acceptability of being asked about mental health in two regions in India: a qualitative study.

BACKGROUND: Mental health conditions are common during pregnancy and the first year after childbirth. Early detection allows timely support and treatment to be offered, but identifying perinatal mental health conditions may be challenging due to stigma and under-recognition of symptoms. Asking about symptoms of mental health conditions during routine antenatal and postnatal appointments can help to identify women at risk. This study explores women's awareness of perinatal mental health conditions, their views on the acceptability of being asked about mental health and any preference for specific assessment tools in two regions in India. METHODS: Focus group discussions (FGDs) were conducted with pregnant, post-partum and non-perinatal women in Kangra, Himachal Pradesh (northern India) and Bengaluru, Karnataka (southern India). Settings included a hospital antenatal clinic and obstetric ward, Anganwadi Centres and Primary Health Centres. FGDs were facilitated, audio-recorded and transcribed. Narratives were coded for emerging themes and analysed using thematic analysis. RESULTS: Seven FGDs including 36 participants were conducted. Emerging themes were: manifestations of and contributors to mental health conditions; challenges in talking about mental health; and the acceptability of being asked about mental health. Difficult familial relationships, prioritising the needs of others and pressure to have a male infant were cited as key stressors. Being asked about mental health was generally reported to be acceptable, though some women felt uncomfortable with questions about suicidality. No preference for any specific assessment tool was reported. CONCLUSIONS: Women face many stressors during the perinatal period including difficult familial relationships and societal pressure to bear a male infant. Being asked about mental health was generally considered to be acceptable, but questions relating to suicidality may be challenging in a community setting, requiring sensitivity by the interviewer. Future studies should assess the acceptability of mental health assessments in 'real world' antenatal and postnatal clinics and explore ways of overcoming the associated challenges in resource-constrained settings.

From Plants to Therapies: Exploring the Pharmacology of Coumestrol for Neurological Conditions.

Neurological disorders are possibly the most prevalent and have been identified to occur among individuals with autism beyond chance. These disorders encompass a diverse range of consequences with neurological causes and have been regarded as a major threat to public mental health. There is no tried-and-true approach for completely protecting the nervous system. Therefore, plant-derived compounds have developed significantly nowadays. Coumestrol (CML) is a potent isoflavone phytoestrogen with a protective effect against neurological dysfunction and has been discovered to be structurally and functionally similar to estrogen. In recent years, more research has been undertaken on phytoestrogens. This research demonstrates the biological complexity of phytoestrogens, which consist of multiple chemical families and function in various ways. This review aimed to explore recent findings on the most significant pharmacological advantages of CML by emphasising neurological benefits. Numerous CML extraction strategies and their pharmacological effects on various neurological disorders, including PD, AD, HD, anxiety, and cognitive impairments, were also documented.

Chemical Diversity and Medicinal Potential of Vitex negundo L.: From Traditional Knowledge to Modern Clinical Trials.

BACKGROUND: In Vedic context, Nirgundi (V. negundo) has been utilized for its anti-inflammatory, analgesic, and wound-healing properties. It has been employed to alleviate pain, treat skin conditions, and address various ailments. The plant's leaves, roots, and seeds have all found applications in traditional remedies. The knowledge of Nirgundi's medicinal benefits has been passed down through generations, and it continues to be a part of Ayurvedic and traditional medicine practices in India.

Insights into the recent advances of agro-industrial waste valorization for sustainable biogas production.

Recent years have seen a transition to a sustainable circular economy model that uses agro-industrial waste biomass waste to produce energy while reducing trash and greenhouse gas emissions. Biogas production from lignocellulosic biomass (LCB) is an alternative option in the hunt for clean and renewable fuels. Different approaches are employed to transform the LCB to biogas, including pretreatment, anaerobic digestion (AD), and biogas upgradation to biomethane. To maintain process stability and improve AD performance, machine learning (ML) tools are being applied in real-time monitoring, predicting, and optimizing the biogas production process. An environmental life cycle assessment approach for biogas production systems is essential to calculate greenhouse gas emissions. The current review presents a detailed overview of the utilization of agro-waste for sustainable biogas production. Different methods of waste biomass processing and valorization are discussed that contribute towards developing an efficient agro-waste to biogas-based circular economy.

Pharmacological modulation of HIF-1 in the treatment of neuropsychiatric disorders.

Hypoxia-inducible factor 1 has been identified as an important therapeutic target in psychiatric illnesses. Hypoxia is a condition in which tissues do not receive enough oxygen, resulting in less oxidative energy production. HIF-1, the master regulator of molecular response to hypoxia, is destabilized when oxygen levels fall. HIF-1, when activated, increases the gene transcription factors that promote adaptive response and longevity in hypoxia. HIF-regulated genes encode proteins involved in cell survival, energy metabolism, angiogenesis, erythropoiesis, and vasomotor control. Multiple genetic and environmental variables contribute to the pathophysiology of psychiatric disease. This review focuses on the most recent findings indicating the role of oxygen deprivation in CNS damage, with strong attention on HIF-mediated pathways. Several pieces of evidence suggested that, in the case of hypoxia, induction and maintenance of HIF-1 target genes may help reduce nerve damage. Major new insights into the molecular mechanisms that control HIF's sensitivity to oxygen are used to make drugs that can change the way HIF works as a therapeutic target for some CNS diseases.

Mutation spectrum and enzyme profiling of G6PD deficiency in neonates of north India: a prospective study.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked disorder with well-established clinical and allelic heterogeneity and ethnic disparity. With ~390,000 annual births with G6PD deficiency in India, it emerges as the most predictable and preventable inbornmetabolic error. Disease prevalence and mutation spectrum have been reasonably reported fromcentral, western and southern parts of India and are mostly retrospective studies.Although prevalence data fromnorth India is available, there is paucity of data on the mutation spectrum and genotype-phenotype correlation (GxP). Thus, we aimed at establishing the clinical and mutation profiles for G6PD, as a part of a large prospective newborn screening study conducted between 2014 and 2016 across hospitals in Delhi, India. G6PD activity levels were measured at 24-48 h of life for ~200,000 neonates using Victor 2D and/or Genomic Screening Processor followed by confirmatory spectrophotometric analysis usingRBClysates of the respective neonates based on clinical symptoms.Asubset of 570 enzyme deficient neonates were screened formutations by polymerase chain reaction-restriction fragment length polymorphismand/or Sanger sequencing.Mediterraneanwas the most common mutation (n=318; 55.8%) with the lowest enzyme activity and most severe phenotype, followed by G6PD Orissa (n=187;32.8%); Kerala-Kalyan (n=25); Jammu (n=24);Mahidol (n=14); Chattam(n=1) andNilgiri/Coimbra (n=1).Of the 163 intramural neonates followed up, 68 developed clinical jaundice. However, no correlation was observed between jaundice and enzyme level. Notable outcome of this first ever prospective screening approach for G6PD deficiency in neonates may help in prediction of disease severity and appropriate timely management.

Recent advances in synthetic strategies and SAR of thiazolidin-4-one containing molecules in cancer therapeutics.

Cancer is one of the life-threatening diseases accountable for millions of demises globally. The inadequate effectiveness of the existing chemotherapy and its harmful effects has resulted in the necessity of developing innovative anticancer agents. Thiazolidin-4-one scaffold is among the most important chemical skeletons that illustrate anticancer activity. Thiazolidin-4-one derivatives have been the subject of extensive research and current scientific literature reveals that these compounds have shown significant anticancer activities. This manuscript is an earnest attempt to review novel thiazolidin-4-one derivatives demonstrating considerable potential as anticancer agents along with a brief discussion of medicinal chemistry-related aspects of these compounds and structural activity relationship studies in order to develop possible multi-target enzyme inhibitors. Most recently, various synthetic strategies have been developed by researchers to get various thiazolidin-4-one derivatives. In this review, the authors highlight the various synthetic, green, and nanomaterial-based synthesis routes of thiazolidin-4-ones as well as their role in anticancer activity by inhibition of various enzymes and cell lines. The detailed description of the existing modern standards in the field presented in this article may be interesting and beneficial to the scientists for further exploration of these heterocyclic compounds as possible anticancer agents.

VSELs and OSCs together sustain oogenesis in adult ovaries and their dysfunction results in age-related senescence, PCOS, POI and cancer.

Multiple studies using single-cell RNA sequencing (scRNAseq) have failed to detect stem cells in adult ovaries. We have maintained that two populations of ovarian stem cells including pluripotent, very small embryonic-like stem cells (VSELs) and tissue-committed 'progenitors' termed ovarian stem cells (OSCs) can easily be detected in Hematoxylin and Eosin-stained ovary surface epithelial (OSE) cells smears prepared from both mice and human ovaries. Most likely the stem cells never get subjected to scRNAseq since they pellet down only by centrifuging cells suspension at 1000 g while cells for scRNAseq were invariably prepared by centrifuging at 200-400 g. A recent article provided further explanation for the failure of scRNAseq to detect ovarian stem cells. Extensive reanalysis of data (generated by scRNAseq) using an advanced software successfully detected OSCs and meiotic markers supporting neo-oogenesis in adult human ovaries. But this article remained critical on the biological relevance of VSELs and their relationship with OSCs. By carefully studying the OSE cells smears (which hold VSELs, OSCs and germ cell nests GCNs), prepared by partial trypsin digestion of intact mice ovaries during different stages of estrus cycle, we have successfully delineated novel functions of VSELs/OSCs in vivo under physiological conditions. VSELs undergo asymmetrical divisions to self-renew and give rise to slightly bigger OSCs which in turn undergo symmetrical divisions and clonal expansion to form GCNs, regular neo-oogenesis and follicle assembly. GCNs have been earlier described in fetal ovaries and during OSE cells culture (from adult ovaries) in response to FSH treatment. Dysfunction of VSELs/OSCs (which express ERα, ERß, FSHR) due to neonatal exposure to endocrine disruption results in ovarian insufficiency and polycystic ovaries. VSELs have also been implicated in ovarian cancer. Age-related ovarian senescence/menopause is also due to dysfunction and blocked differentiation of VSELs/OSCs. These novel findings in vivo along with abundant in vitro and lineage tracing studies data in published literature provides huge scope for further research, offers novel avenues to manage ovarian pathologies and calls for re-writing of textbooks.

Artificial intelligence based approach for categorization of COVID-19 ECG images in presence of other cardiovascular disorders.

Coronavirus disease (COVID-19) is a class of SARS-CoV-2 virus which is initially identified in the later half of the year 2019 and then evolved as a pandemic. If it is not identified in the early stage then the infection and mortality rates increase with time. A timely and reliable approach for COVID-19 identification has become important in order to prevent the disease from spreading rapidly. In recent times, many methods have been suggested for the detection of COVID-19 disease have various flaws, to increase diagnosis performance, fresh investigations are required. In this article, automatically diagnosing COVID-19 using ECG images and deep learning approaches like as Visual Geometry Group (VGG) and AlexNet architectures have been proposed. The proposed method is able to classify between COVID-19, myocardial infarction, normal sinus rhythm, and other abnormal heart beats using Lead-II ECG image only. The efficacy of the technique proposed is validated by using a publicly available ECG image database. We have achieved an accuracy of 77.42% using Alexnet model and 75% accuracy with the help of VGG19 model.

Computational Design of Plant-Based Antistress Agents Targeting Nociceptin Receptor.

Stress is the body's reaction to the challenges it faces, and it produces a multitude of chemical molecules known as stressors as a result of these reactions. It's also a misalignment of the sympathetic and parasympathetic nervous systems causing changes in a variety of physiological reactions and perhaps leading to stress disorders. The reduction in neurotransmitter & neurohormonal hormones is mainly governed by the nociceptin receptor as G-protein coupled receptor and increased the level of reactive oxygen species. Various synthetic medicines that target nociceptin receptors were utilized to reduce the effects of stress but they come up with a variety of side effects. Because of the widespread utilization and renewed interest in medicinal herbal plants considered to be alternative antistress therapy. Our present work is an approach to decipher the molecular nature of novel herbal leads by targeting nociceptin receptor, under which herbal compounds were screened and validated through in-silico methods. Among screened leads, withanolide-B showed stable association in the active site of the nociceptin receptor as an antistress agent with no side effects. Furthermore, the selected lead was also evaluated for stability by molecular dynamic stimulation as well as for pharmacokinetics and toxicity profile. It has been concluded stable conformation of withanolide-B without presence of any major toxic effects. As a result, the in silico molecular docking technique is a highly successful method for selecting a prospective herbal lead molecule with respect to a specific target, and future research can pave the way for further exploration in the drug development field.

Assessment of key regulatory genes and identification of possible drug targets for Leprosy (Hansen's disease) using network-based approach.

Leprosy is a major health concern and continues to be a source of fear and stigma among people worldwide. Despite remarkable achievements in the treatment, understanding of pathogenesis and transmission, epidemiology of leprosy still remains inadequate. The prolonged incubation period, slow rates of occurrence in those exposed and deceptive clinical presentation pose challenges to develop reliable strategies to stop transmission. Hence, there is a need for improved diagnostics and therapies to prevent mortality caused by leprosy. The objectives of this study are to identify significant genes from protein-protein interactions (PPIs) network of leprosy and to choose the most effective therapeutic targets. Fifty genes related with leprosy were discovered by literature mining. These genes were used to construct a primary network. Leading Eigen Vector method was used to break down the primary network into various sub-networks or communities. It was found that the primary network was divided into many sub-networks at the 6 levels. Seed genes were traced at each level till key regulatory genes were identified. Three seed genes, namely, GNAI3, NOTCH1, and HIF1A, were able to make their way till the final motif stage. These genes along with their interacting partners were considered key regulators of the leprosy network. This study provides leprosy-associated key genes which can lead to improved diagnosis and therapies for leprosy patients.

Phytoplankton community shift in response to experimental Cu addition at the elevated CO2 levels (Arabian Sea, winter monsoon).

Understanding phytoplankton community shifts under multiple stressors is becoming increasingly important. Among other combinations of stressors, the impact of trace metal toxicity on marine phytoplankton under the ocean acidification scenario is an important aspect to address. Such multiple stressor studies are rare from the Arabian Sea, one of the highest productive oceanic provinces within the North Indian Ocean. We studied the interactive impacts of copper (Cu) and CO2 enrichment on two natural phytoplankton communities from the eastern and central Arabian Sea. Low dissolved silicate (DSi < 2 µM) favoured smaller diatoms (e.g. Nitzschia sp.) and non-diatom (Phaeocystis). CO2 enrichment caused both positive (Nitzschia sp. and Phaeocystis sp.) and negative (Cylindrotheca closterium, Navicula sp., Pseudo-nitzschia sp., Alexandrium sp., and Gymnodinium sp.) growth impacts. The addition of Cu under the ambient CO2 level (A-CO2) hindered cell division in most of the species, whereas Chla contents were nearly unaffected. Interestingly, CO2 enrichment seemed to alleviate Cu toxicity in some species (Nitzschia sp., Cylindrotheca closterium, Guinardia flaccida, and Phaeocystis) and increased their growth rates. This could be related to the cellular Cu demand and energy budget at elevated CO2 levels. Dinoflagellates were more sensitive to Cu supply compared to diatoms and prymnesiophytes and could be related to the unavailability of prey. Such community shifts in response to the projected ocean acidification, oligotrophy, and Cu pollution may impact trophic transfer and carbon cycling in this region.