Emerging challenges in antimicrobial resistance: implications for pathogenic microorganisms, novel antibiotics, and their impact on sustainability.

Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals.

A Comprehensive Guide to the Development, Evaluation, and Future Prospects of Self-nanoemulsifying Drug Delivery Systems for Poorly Water-soluble Drugs.

Self-Nano Emulsifying Drug Delivery Systems (SNEDDS) are novel formulations that can enhance the solubility and bioavailability of poorly water-soluble drugs. SNEDDS are composed of lipids, surfactants, co-solvents, and drugs and can spontaneously form nanoemulsions when mixed with water under mild agitation. SNEDDS can be formulated as liquid or solid dosage forms and can improve drug absorption by increasing the interfacial area, protecting the drug from degradation, and facilitating lymphatic transport. SNEDDS is characterized by various parameters such as particle size, zeta potential, droplet morphology, emulsification efficiency, drug solubility, and stability. SNEDDS offers several advantages over conventional dosage forms, such as dose reduction, faster onset of action, reduced variability, versatility, and ease of formulation. However, SNEDDS also face some limitations and challenges, such as drug precipitation, cost-effectiveness, compatibility with capsule shells, and lack of predictive in vitro models. SNEDDS has a promising future in the field of pharmaceuticals, especially for personalized medicine and targeted drug delivery.

Degradation of SDS by psychrotolerant Staphylococcus saprophyticus and Bacillus pumilus isolated from Southern Ocean water samples.

Bioremediation of surfactants in water bodies holds significant ecological importance as they are contaminants of emerging concern posing substantial threats to the aquatic environment. Microbes exhibiting special ability in terms of bioremediation of contaminants have always been reported to thrive in extraordinary environmental conditions that can be extreme in terms of temperature, lack of nutrients, and salinity. Therefore, in the present investigation, a total of 46 bacterial isolates were isolated from the Indian sector of the Southern Ocean and screened for degradation of sodium dodecyl sulphate (SDS). Further, two Gram-positive psychrotolerant bacterial strains, ASOI-01 and ASOI-02 were identified with significant SDS degradation potential. These isolates were further studied for growth optimization under different environmental conditions. The strains were characterized as Staphylococcus saprophyticus and Bacillus pumilus based on morphological, biochemical, and molecular (16S RNA gene) characteristics. The study reports 88.9% and 93.4% degradation of SDS at a concentration of 100 mgL-1, at 20 °C, and pH 7 by S. saprophyticus ASOI-01 and B. pumilus ASOI-02, respectively. The experiments were also conducted in wastewater samples where a slight reduction in degradation efficiency was observed with strains ASOI-01 and ASOI-02 exhibiting 76.83 and 64.93% degradation of SDS respectively. This study infers that these bacteria can be used for the bioremediation of anionic surfactants from water bodies and establishes the potential of extremophilic microbes for the utilization of sustainable wastewater management.

Nurturing Empathy through Arts, Literature, and Role Play for Postgraduate Trainees of Ophthalmology.

Background and Purpose: Empathy is essential in patient-centered compassionate health care. Lack of formal training, workload, patient factors, and digitalization have been attributed to its regression. Empathy can be nurtured by educational interventions. A structured empathy education module for postgraduate trainees is not available in India. The aim for this research was to develop, deliver, and evaluate one for ophthalmology postgraduate trainees. Methodology: This interventional study was conducted in the tertiary ophthalmology department of Western India during 2022-2023. Four workshops comprising of interactive lectures, literature, creative arts, and role plays were delivered with trained facilitators. Data from surveys for trainee self-assessment, patient perception of trainee empathy, pre-post knowledge test, and trainee and facilitator feedback were collected and analyzed. Results: Seventy-nine ophthalmology postgraduate trainees participated in this intervention. Excessive workload and lack of training were shared as the barriers to empathetic care. Trainees showed improved knowledge, skills, and attitude in empathy after the workshops. The facilitators and trainees were satisfied with the learning goals, execution, utility, feasibility, and relevance of the workshops. Ninety-three percent trainees want this module to be a part of postgraduate curriculum. Conclusion: This study substantiates the use of structured interactive training for cultivating empathy in postgraduate trainees. Barriers against empathy were identified and can be mitigated by restorative measures. Literature, arts, and role plays are the effective education tools for empathy.

Potential use of cidofovir, brincidofovir, and tecovirimat drugs in fighting monkeypox infection: recent trends and advancements.

Recent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease's understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox.

The Pharmacological Implications of Flavopiridol: An Updated Overview.

Flavopiridol is a flavone synthesized from the natural product rohitukine, which is derived from an Indian medicinal plant, namely Dysoxylum binectariferum Hiern. A deeper understanding of the biological mechanisms by which such molecules act may allow scientists to develop effective therapeutic strategies against a variety of life-threatening diseases, such as cancer, viruses, fungal infections, parasites, and neurodegenerative diseases. Mechanistic insight of flavopiridol reveals its potential for kinase inhibitory activity of CDKs (cyclin-dependent kinases) and other kinases, leading to the inhibition of various processes, including cell cycle progression, apoptosis, tumor proliferation, angiogenesis, tumor metastasis, and the inflammation process. The synthetic derivatives of flavopiridol have overcome a few demerits of its parent compound. Moreover, these derivatives have much improved CDK-inhibitory activity and therapeutic abilities for treating severe human diseases. It appears that flavopiridol has potential as a candidate for the formulation of an integrated strategy to combat and alleviate human diseases. This review article aims to unravel the potential therapeutic effectiveness of flavopiridol and its possible mechanism of action.

Corrigendum: Fabrication and evaluation of herbal beads to slow cell ageing.

[This corrects the article DOI: 10.3389/fbioe.2022.1025405.].

Primary Small Cell Neuroendocrine Carcinoma of nasopharynx with metastatic cervical lymph nodes: an exceedingly rare entity with review of literature.

Small cell neuroendocrine carcinoma of nasopharynx is extremely rare and displays aggressive nature with a poor prognosis. Neuroendocrine tumours rarely arise from the head and neck region and pose a diagnostic and management challenge. In English literature, only 16 cases of primary small cell neuroendocrine carcinoma of nasopharynx have been reported so far; and to the best of our knowledge, this is the seventeenth case and second in the younger age group. Here, we report the case of an adolescent male patient who presented with nasal blockage, repeated episodes of epistaxis and neck swellings. After proper diagnostic workup, the diagnosis of small cell neuroendocrine carcinoma of nasopharynx was made. The patient was treated with chemotherapy, followed by radiotherapy. Imaging investigation executed after the end of the treatment exhibited complete remission of the disease. The patient is kept under active surveillance with no signs of relapse at present.

Guidance document: risk assessment of patients with cirrhosis prior to elective non-hepatic surgery.

As a result of the increasing incidence of cirrhosis in the UK, more patients with chronic liver disease are being considered for elective non-hepatic surgery. A historical reluctance to offer surgery to such patients stems from general perceptions of poor postoperative outcomes. While this is true for those with decompensated cirrhosis, selected patients with compensated early-stage cirrhosis can have good outcomes after careful risk assessment. Well-recognised risks include those of general anaesthesia, bleeding, infections, impaired wound healing, acute kidney injury and cardiovascular compromise. Intra-abdominal or cardiothoracic surgery are particularly high-risk interventions. Clinical assessment supplemented by blood tests, imaging, liver stiffness measurement, endoscopy and assessment of portal pressure (derived from the hepatic venous pressure gradient) can facilitate risk stratification. Traditional prognostic scoring systems including the Child-Turcotte-Pugh and Model for End-stage Liver Disease are helpful but may overestimate surgical risk. Specific prognostic scores like Mayo Risk Score, VOCAL-Penn and ADOPT-LC can add precision to risk assessment. Measures to mitigate risk include careful management of varices, nutritional optimisation and where possible addressing any ongoing aetiological drivers such as alcohol consumption. The role of portal decompression such as transjugular intrahepatic portosystemic shunting can be considered in selected high-risk patients, but further prospective study of this approach is required. It is of paramount importance that patients are discussed in a multidisciplinary forum, and that patients are carefully counselled about potential risks and benefits.

Correction to: Identification and validation of reference genes in vetiver (Chrysopogon zizanioides) root transcriptome.

[This corrects the article DOI: 10.1007/s12298-023-01315-7.].

A critical review on therapeutic approaches of CRISPR-Cas9 in diabetes mellitus.

Diabetes mellitus (D.M.) is a common metabolic disorder caused mainly by combining two primary factors, which are (1) defects in insulin production by the pancreatic ß-cells and (2) responsiveness of insulin-sensitive tissues towards insulin. Despite the rapid advancement in medicine to suppress elevated blood glucose levels (hyperglycemia) and insulin resistance associated with this hazard, a demand has undoubtedly emerged to find more effective and curative dimensions in therapeutic approaches against D.M. The administration of diabetes treatment that emphasizes insulin production and sensitivity may result in unfavorable side effects, reduced adherence, and potential treatment ineffectiveness. Recent progressions in genome editing technologies, for instance, in zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR-Cas)-associated nucleases, have greatly influenced the gene editing technology from concepts to clinical practices. Improvements in genome editing technologies have also opened up the possibility to target and modify specific genome sequences in a cell directly. CRISPR/Cas9 has proven effective in utilizing ex vivo gene editing in embryonic stem cells and stem cells derived from patients. This application has facilitated the exploration of pancreatic beta-cell development and function. Furthermore, CRISPR/Cas9 enables the creation of innovative animal models for diabetes and assesses the effectiveness of different therapeutic strategies in treating the condition. We, therefore, present a critical review of the therapeutic approaches of the genome editing tool CRISPR-Cas9 in treating D.M., discussing the challenges and limitations of implementing this technology.

Guidelines for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA): Joint Indian Chest Society (ICS)/Indian Association for Bronchology (IAB) recommendations.

Over the past decade, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an indispensable tool in the diagnostic armamentarium of the pulmonologist. As the expertise with EBUS-TBNA has evolved and several innovations have occurred, the indications for its use have expanded. However, several aspects of EBUS-TBNA are still not standardized. Hence, evidence-based guidelines are needed to optimize the diagnostic yield and safety of EBUS-TBNA. For this purpose, a working group of experts from India was constituted. A detailed and systematic search was performed to extract relevant literature pertaining to various aspects of EBUS-TBNA. The modified GRADE system was used for evaluating the level of evidence and assigning the strength of recommendations. The final recommendations were framed with the consensus of the working group after several rounds of online discussions and a two-day in-person meeting. These guidelines provide evidence-based recommendations encompassing indications of EBUS-TBNA, pre-procedure evaluation, sedation and anesthesia, technical and procedural aspects, sample processing, EBUS-TBNA in special situations, and training for EBUS-TBNA.

A Novel Study on Anionic Surfactant Degradation Potential of Psychrophillic and Psychrotolerant Pseudomonas spp. Identified from Surfactant-contaminated River Water.

The Yamuna River, a tributary of the holy Ganga, is heavily polluted in the Delhi-NCR region, India and has been gaining attention due to the excessive foaming of the river over the past few years. This can be directly or indirectly related to the overuse of surfactants and the discharge of untreated domestic and textile wastewater into the river. To determine the surfactant load and investigate potential surfactant-degrading bacteria in the region, 96 water samples from four sites in the Okhla Barrage stretch of the river were collected and analysed. The results showed that the selected sites have surfactant concentrations more than the permissible limit (1.00 mgL-1). Also, at most of the sites, the concentration crossed the desirable limit of BIS (0.2 mgL-1) during the period of analysis. The concentration of anionic surfactant reported in the region was found in the range of 0.29 mgL-1 and 2.83 mgL-1. A total of 38 different bacteria were isolated using selective media from the same water samples, out of which 7 bacterial isolates were screened for sodium dodecyl sulphate (SDS) tolerance activity. Based on 16S rRNA gene sequencing, 2 species, namely Pseudomonas koreensis YRW-02 and Pseudomonas songnenensis YRW-05 have been identified and their degradation potential was assessed at different SDS concentrations. The results showed that our strains YRW-02 and YRW-05 degraded 78.29 and 69.24% of SDS respectively. Growth optimization was also performed at different substrate concentrations, pH, and temperature to investigate optimum degradation conditions. This study plays a significant role in assessing the surfactant load and also gives a promising background for future use in in-situ bioremediation experiments.

Cyanobacterial compound Tolyporphine K as an inhibitor of Apo-PBP (penicillin-binding protein) in A. baumannii and its ADME assessment.

Antibiotic-resistant Acinetobacter baumannii, is a common pathogen found in hospital settings and has become nosocomial due to its high infection-causing tendency amongst ICU patients. The present study explores the cyanocompoundswhich were capable to inhibit the Penicillin Binding Protein of A. baumannii through molecular docking, ADMET, and molecular dynamicssimulation strategy. A database having structural and origin details was generated for 85 bioactive compounds in MS Excel. The 3-D structures weredownloaded from the PubChem database and minimized. The receptor protein was minimized and validated for structure correctness. The database was screened against the penicillin-binding protein of A. baumannii through PyRx software. The top 5 compounds including the control molecule werefurther redocked to the receptor molecule through Autodock Vina software. The molecule pose having the highest affinity was further subjected to 100ns MD- simulation and simultaneously the in-vitro activity of the methanol extract and hexane extract was checked through agar well diffusion assay.Docking studies indicate Tolyporphine K to be a lead molecule which was further assessed through Molecular dynamics and MM/PBSA. The in-silicoresults suggested that the protein-ligand complex was found to be stable over the 100 ns trajectory with a binding free energy of -8.56 Kcalmol-1. Theligand did not induce any major structural conformation in the protein moiety and was largely stabilized by hydrophobic interactions. The bioactivityscore and ADME properties of the compounds were also calculated. The in-vitro agar well diffusion assay showed a moderate zone of inhibition of12.33mm. The results indicate that the compound Tolyporphin- K could be a potential inhibitor of penicillin-binding protein in A. baumannii. Yet furtherwork needs to be done to have a more concrete basis for the pathway of inhibition.Communicated by Ramaswamy H. Sarma.

Identification and validation of reference genes in vetiver (Chrysopogon zizanioides) root transcriptome.

Vetiver [Vetiveria zizanioides (L.) Roberty] is a perennial C-4 grass traditionally valued for its aromatic roots/root essential oil. Owing to its deep penetrating web-forming roots, the grass is now widely used across the globe for phytoremediation and the conservation of soil and water. This study has used the transcriptome data of vetiver roots in its two distinct geographic morphotypes (North Indian type A and South Indian type B) for reference gene(s) identification. Further, validation of reference genes using various abiotic stresses such as heat, cold, salt, and drought was carried out. The de novo assembly based on differential genes analysis gave 1,36,824 genes (PRJNA292937). Statistical tests like RefFinder, NormFinder, BestKeeper, geNorm, and Delta-Ct software were applied on 346 selected contigs. Eleven selected genes viz., GAPs, UBE2W, RP, OSCam2, MUB, RPS, Core histone 1, Core histone 2, SAMS, GRCWSP, PLDCP along with Actin were used for qRT-PCR analysis. Finally, the study identified the five best reference genes GAPs, OsCam2, MUB, Core histone 1, and SAMS along with Actin. The two optimal reference genes SAMS and Core histone 1 were identified with the help of qbase + software. The findings of the present analyses have value in the identification of suitable reference gene(s) in transcriptomic and molecular data analysis concerning various phenotypes related to abiotic stress and developmental aspects, as well as a quality control measure in gene expression experiments. Identifying reference genes in vetiver appears important as it allows for accurate normalization of gene expression data in qRT-PCR experiments. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01315-7.

Wogonin, as a potent anticancer compound: From chemistry to cellular interactions.

Chinese native medicine Scutellaria baicalensis Georgi, also referred to as Chinese skullcap or Huang-Qin, is frequently used to treat cancer, viral infections, and seizures. This plant's abundance of flavones (wogonoside) and their related aglycones (wogonin) is responsible for many of its pharmacologic effects. A significant ingredient in S. baicalensis that has been the subject of the most research is wogonin. Numerous preclinical investigations revealed that wogonin suppresses tumor growth by cell cycle arrest, stimulating cell death and preventing metastasis. This review focuses on a complete overview of published reports that suggest chemopreventive action of wogonin and the mechanistic insights behind these neoplastic activities. It also emphasizes the synergistic improvements made by wogonin in chemoprevention. The factual data in this mini-review stimulate additional research on chemistry and toxicological profile of wogonin to confirm its safety issues. This review will encourage researchers to generalize the merits of wogonin to be used as potential compound for cancer treatment.

Ethnopharmacological Potential of Phytochemicals and Phytogenic Products against Human RNA Viral Diseases as Preventive Therapeutics.

RNA viruses have been the most destructive due to their transmissibility and lack of control measures. Developments of vaccines for RNA viruses are very tough or almost impossible as viruses are highly mutable. For the last few decades, most of the epidemic and pandemic viral diseases have wreaked huge devastation with innumerable fatalities. To combat this threat to mankind, plant-derived novel antiviral products may contribute as reliable alternatives. They are assumed to be nontoxic, less hazardous, and safe compounds that have been in uses in the beginning of human civilization. In this growing COVID-19 pandemic, the present review amalgamates and depicts the role of various plant products in curing viral diseases in humans.