Search

Drug-induced liver injury (DILI) has been a significant challenge in drug discovery, often leading to clinical trial failures and necessitating drug withdrawals. Over the last decade, the existing suite of in vitro proxy-DILI assays has generally improved at identifying compounds with hepatotoxicity. However, there is considerable interest in enhancing the in silico prediction of DILI because it allows for evaluating large sets of compounds more quickly and cost-effectively, particularly in the early stages of projects. In this study, we aim to study ML models for DILI prediction that first predict nine proxy-DILI labels and then use them as features in addition to chemical structural features to predict DILI. The features include in vitro (e.g., mitochondrial toxicity, bile salt export pump inhibition) data, in vivo (e.g., preclinical rat hepatotoxicity studies) data, pharmacokinetic parameters of maximum concentration, structural fingerprints, and physicochemical parameters. We trained DILI-prediction models on 888 compounds from the DILI data set (composed of DILIst and DILIrank) and tested them on a held-out external test set of 223 compounds from the DILI data set. The best model, DILIPredictor, attained an AUC-PR of 0.79. This model enabled the detection of the top 25 toxic compounds (2.68 LR+, positive likelihood ratio) compared to models using only structural features (1.65 LR+ score). Using feature interpretation from DILIPredictor, we identified the chemical substructures causing DILI and differentiated cases of DILI caused by compounds in animals but not in humans. For example, DILIPredictor correctly recognized 2-butoxyethanol as nontoxic in humans despite its hepatotoxicity in mice models. Overall, the DILIPredictor model improves the detection of compounds causing DILI with an improved differentiation between animal and human sensitivity and the potential for mechanism evaluation. DILIPredictor required only chemical structures as input for prediction and is publicly available at https://broad.io/DILIPredictor for use via web interface and with all code available for download.

S100 proteins comprise a family of structurally related proteins that are calcium-sensitive. S100 proteins have been found to play various roles in regulation of cell apoptosis, cell proliferation and differentiation, cell migration and invasion, energy metabolism, calcium homeostasis, protein phosphorylation, anti-microbial activity and inflammation in a variety of cell types. While the specific function of many S100 proteins remains unknown, some of the S100 proteins serve as disease biomarkers as well as possible therapeutic targets in skin diseases. Interface dermatitis (ID) is a histopathological term that covers many different skin conditions including cutaneous lupus erythematosus, lichen planus, and dermatomyositis. These pathologies share similar histological features, which include basal cell vacuolization and lymphocytic infiltration at the dermal-epidermal junction. In this review, we summarize how the S100 protein family contributes to both homeostatic and inflammatory processes in the skin. We also highlight the role of S100 proteins in neuronal signalling, describing how this might contribute to neuroimmune interactions in ID and other skin pathologies. Last, we discuss what is known about the S100 family proteins as both biomarkers and potential treatment targets in specific pathologies., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Wound healing, particularly for chronic wounds, presents a considerable difficulty due to differences in biochemical and cellular processes that occur in different types of wounds. Recent technological breakthroughs have notably advanced the understanding of diagnostic and therapeutic approaches to wound healing. The evolution in wound care has seen a transition from traditional textile dressings to a variety of advanced alternatives, including self-healing hydrogels, hydrofibers, foams, hydrocolloids, environment responsive dressings, growth factor-based therapy, bioengineered skin substitutes, and stem cell and gene therapy. Technological advancements, such as 3D printing and electronic skin (e-skin) therapy, contribute to the customization of wound healing. Despite these advancements, effectively managing chronic wounds remains challenging. This necessitates the development of treatments that consider performance, risk-benefit balance, and cost-effectiveness. This review discusses innovative strategies for the healing of chronic wounds. Incorporating biomarkers into advanced dressings, coupled with corresponding biosensors and drug delivery formulations, enables the theranostic approach to the treatment of chronic wounds. Furthermore, integrating advanced dressings with power sources and user interfaces like near-field communication, radio frequency identification, and Bluetooth enhances real-time monitoring and on-demand drug delivery. It also provides a thorough evaluation of the advantages, patient compliance, costs, and durability of advanced dressings, emphasizing smart formulations and their preparation methods.

Background: Drug research is increasingly using Network Pharmacology (NP) to tackle complex conditions like Metabolic Syndrome (MetS), which is characterized by obesity, hyperglycemia, and dyslipidemia. Single-action drugs are inadequate to treat MetS, which is marked by a range of complications including glucose intolerance, hyperlipidemia, mitochondrial dysfunction, and inflammation., Objectives: To analyze Chandraprabha vati using Network Pharmacology to assess its potential in alleviating MetS-related complications., Material and Methods: The genes related to MetS, inflammation, and the target genes of the CPV components were identified using network pharmacology tools like DisgNET and BindingDB. Followed by mapping of the CPV target genes with the genes implicated in MetS and inflammation to identify putative potential targets. Gene ontology, pathway enrichment analysis, and STRING database were employed for further exploration. Furthermore, drug-target-protein interactions network were visualized using Cytoscape 3.9.1., Results: The results showed that out of the 225 target genes of the CPV components, 33 overlapping and 19 non-overlapping genes could be potential targets for MetS. Similarly, 14 overlapping and 7 non-overlapping genes could be potential targets for inflammation. The CPV bioactives target genes were found to be involved in lipid and insulin homeostasis via several pathways revealed by the pathway analysis. The importance of CPV in treating MetS was supported by GO enrichment data; this could be due to its potential to influence pathways linked to metabolism, ER stress, mitochondrial dysfunction, oxidative stress, and inflammation., Conclusions: These results offer a promising approach to developing treatment and repurposing CPV for complex conditions such as MetS., Competing Interests: Conflict of 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Suicide is an important public health problem, fundamentally affecting the younger population and responding to multiple biological, psychological, and social causes. The objective of this study was to characterize changes in suicide mortality, suicide methods, and years of potential life lost from 2005 to 2019 in Paraguay. This observational, descriptive study used data from the Vital Statistics Information Subsystem of the Ministry of Public Health and Social Welfare. The average mortality rate from suicide was 4.9 per 100,000 inhabitants, with an increase from 4.2 between 2005 and 2009 to 5.8 from 2014 to 2019. Suicide was more common in men (75%) than in women. In men, the highest mortality rate was observed among those 20-24 years old, whereas in women, the ages most affected were the 15-19-year-old age group. The most-used method for suicide was hanging. The most frequent place of suicide occurrence was at home (73%). The seasonality of suicide occurrence showed a slight increase in the spring-summer months compared with autumn-winter (53% vs. 47%). The rate of potential years of life lost statistically significantly increased from 2005 to 2019. Public health measures need to be implemented to investigate the underlying reasons and implement interventions in the population to decrease suicide mortality in Paraguay.

Cilia are microtubule-based sensory organelles present in a number of eukaryotic cells. Mutations in the genes encoding ciliary proteins cause ciliopathies in humans. A-kinase anchoring proteins (AKAPs) tether ciliary signaling proteins such as protein kinase A (PKA). The dimerization and docking domain (D/D) on the RIIα subunit of PKA interacts with AKAPs. Here, we show that AKAP240 from the central-pair microtubules of Chlamydomonas reinhardtii cilia uses two C-terminal amphipathic helices to bind to its partner FAP174, an RIIα-like protein with a D/D domain at the N-terminus. Co-immunoprecipitation using anti-FAP174 antibody with an enriched central-pair microtubule fraction isolated seven interactors whose mass spectrometry analysis revealed proteins from the C2a (FAP65, FAP70, and FAP147) and C1b (CPC1, HSP70A, and FAP42) microtubule projections and FAP75, a protein whose sub-ciliary localization is unknown. Using RII D/D and FAP174 as baits, we identified two additional AKAPs (CPC1 and FAP297) in the central-pair microtubules., (© 2023 Federation of European Biochemical Societies.)

Metal-free near-infrared absorbing photosensitizers (PS) have been considered promising candidates for photodynamic therapy. Curcumin, curcuminoid, and its derivatives have therapeutic values due to their anti-inflammatory, antifungal, and antiproliferative properties. Curcuminoid-BF 2 chelates have also been studied as cell imaging probes, however, their applications in photodynamic therapy are rare. In this article, we describe the synthesis and therapeutic evaluation of quinolizidine fused curcuminoid-BF2 chelate (Quinolizidine CUR-BF 2 ) containing an acid-sensitive group. This donor-acceptor-donor curcuminoid-BF2 derivative exhibits absorption and emission in the deep red region with an absorption band maximum of ∼647 nm and a weak emission band at approximately 713 nm. It is interesting to note that this derivative has a high molar extinction coefficient (164,655 M -1 cm -1 ). Quinolizidine CUR-BF 2 possesses intramolecular charge transfer properties, facilitating the production of singlet oxygen ( 1 O 2 ), which plays a crucial role in cell death. Additionally, Quinolizidine CUR-BF 2 can enable the selective release of active ingredients in an acidic medium (pH 5). Furthermore, the nanoaggregates of PS were prepared by encapsulating Quinolizidine CUR-BF 2 within Pluronic F127 block co-polymer for better water-dispersibility and enhanced cellular uptake. Dark cytotoxicity of nanoaggregates was found to be negligible, whereas they exhibited significant photoinduced cytotoxicity towards cancer cells (MCF-7 and A549) under irradiation of 635 nm light. Further, the cell death pathway using Quinolizidine CUR-BF 2 nanoaggregates as PS is found to occur through apoptosis. Specifically, the present study deals with the successful preparation of Quinolizidine CUR-BF 2 nanoaggregates for enhanced water-dispersibility and cellular uptake as well as the efficacy evaluation of developed nanoaggregates for photodynamic therapy., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

A simple strategy to modulate the singlet-triplet energy gap in 3,6-diaryl- N -acetophenylcarbazole derivatives is developed. Different substituents significantly influenced Δ E ST , which is correlated for the first time with the singlet-triplet state dipole moments. Phosphorescence at ambient conditions in powder form ( τ is up to 248 μs) and ultra long lifetime (up to 2.2 s) at 77 K is observed.

Arsenic pollution and its allied impacts on health are widely reported and have gained global attention in the last few decades. Although the natural distribution of arsenic is limited, anthropogenic activities have increased its mobility to distant locations, thereby increasing the number of people affected by arsenic pollution. Arsenic has a complex biogeochemical cycle which has a significant role in pollution. Therefore, this review paper has comprehensively analysed the biogeochemical cycle of arsenic which can dictate the occurrence of arsenic pollution. Considering the toxicity and nature of arsenic, the present work has also analysed the current status of arsenic pollution around the world. It is noted that the south of Asia, West-central Africa, west of Europe and Latin America are major hot spots of arsenic pollution. Bibliometric analysis was performed by using scopus database with specific search for keywords such as arsenic pollution, health hazards to obtain the relevant data. Scopus database was searched for the period of 20 years from year 2003-2023 and total of 1839 articles were finally selected for further analysis using VOS viewer. Bibliometric analysis of arsenic pollution and its health hazards has revealed that arsenic pollution is primarily caused by anthropogenic sources and the key sources of arsenic exposure are drinking water, sea food and agricultural produces. Arsenic pollution was found to be associated with severe health hazards such as cancer and other health issues. Thus considering the severity of the issue, few sustainable remediation technologies such as adsorption using microbes, biological waste material, nanomaterial, constructed wetland, phytoremediation and microorganism bioremediation are proposed for treating arsenic pollution. These approaches are environmentally friendly and highly sustainable, thus making them suitable for the current scenario of environmental crisis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Bhupendra Pushkar reports financial support was provided by Ramniklal S. Gosalia & Co., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Environmental factors such as exposure to ionizing radiations, certain environmental pollutants, and toxic chemicals are considered as risk factors in the development of breast cancer. Triple-negative breast cancer (TNBC) is a molecular variant of breast cancer that lacks therapeutic targets such as progesterone receptor, estrogen receptor, and human epidermal growth factor receptor-2 which makes the targeted therapy ineffective in TNBC patients. Therefore, identification of new therapeutic targets for the treatment of TNBC and the discovery of new therapeutic agents is the need of the hour. In this study, CXCR4 was found to be highly expressed in majority of breast cancer tissues and metastatic lymph nodes derived from TNBC patients. CXCR4 expression is positively correlated with breast cancer metastasis and poor prognosis of TNBC patients suggesting that suppression of CXCR4 expression could be a good strategy in the treatment of TNBC patients. Therefore, the effect of Z-guggulsterone (ZGA) on the expression of CXCR4 in TNBC cells was examined. ZGA downregulated protein and mRNA expression of CXCR4 in TNBC cells and proteasome inhibition or lysosomal stabilization had no effect on the ZGA-induced CXCR4 reduction. CXCR4 is under the transcriptional control of NF-κB, whereas ZGA was found to downregulate transcriptional activity of NF-κB. Functionally, ZGA downmodulated the CXCL12-driven migration/invasion in TNBC cells. Additionally, the effect of ZGA on growth of tumor was investigated in the orthotopic TNBC mice model. ZGA presented good inhibition of tumor growth and liver/lung metastasis in this model. Western blotting and immunohistochemical analysis indicated a reduction of CXCR4, NF-κB, and Ki67 in tumor tissues. Computational analysis suggested PXR agonism and FXR antagonism as targets of ZGA. In conclusion, CXCR4 was found to be overexpressed in majority of patient-derived TNBC tissues and ZGA abrogated the growth of TNBC tumors by partly targeting the CXCL12/CXCR4 signaling axis., 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.)

Major challenges in current cancer chemotherapy include drug resistance, low efficacy and non-selectivity, resulting in undesirable side effects. In this study, we demonstrate a solution to these challenges that involves a dual targeting approach for tumors that overexpress CD44 receptors. The approach employs a nano-formulation (tHAC-MTX nano assembly), fabricated from hyaluronic acid (HA), the natural ligand for CD44, conjugated with methotrexate (MTX) and complexed with the thermoresponsive polymer 6-O-carboxymethylchitosan (6-OCMC) graft poly(N-isopropylacrylamide) [6-OCMC-g-PNIPAAm]. The thermoresponsive component was designed to have a lower critical solution temperature of 39 °C (the temperature of tumor tissues). In-vitro drug release studies reveal faster release of the drug at the higher temperatures of the tumor tissue likely due to the conformation changes in the thermoresponsive component of the nano assembly. Drug release was also enhanced in the presence of hyaluronidase enzyme. Higher cellular uptake and greater cytotoxicity of the nanoparticles were demonstrated in cancer cells that overexpress CD44 receptors suggesting a receptor binding and cellular uptake mechanism. Such nano-assemblies which incorporate multiple targeting mechanisms have the potential to improve efficacy and decrease side effects of cancer chemotherapy., Competing Interests: Declaration of competing interest The authors confirm that they have no known financial or interpersonal conflicts that would have an impact on the research presented in this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

H 8 -BINOL, a partially reduced form of BINOL, is widely employed in a broad array of organocatalyzed asymmetric methodologies. Over the last 25 years, asymmetric organocatalysis has witnessed an incredible improvement, and an advancement still continues to get a single enantio-enriched product. The broad-spectrum applications of H 8 -BINOL organocatalyst in C-C bond formation, C-heteroatom bond construction, name reactions, pericyclic reactions, and one pot and multicomponent reaction are attracting the attention of researchers. A diversified unique H 8 -BINOL-based catalyst has been synthesized and screened for catalytic activity. In this Review we frame out the H 8 -BINOL catalyzed novel discoveries from the last two decades., Competing Interests: The author declares no competing financial interest., (© 2023 The Author. Published by American Chemical Society.)

Ultraviolet C (UV-C) radiation induces apoptosis in mammalian cells via the mitochondrion-mediated pathway. The Bcl-2 family of proteins are the regulators of the mitochondrial pathway of apoptosis and appears responsive to UV-C radiation. It is unknown how the structure and, effectively, the function of these proteins are directly impacted by UV-C exposure. Here, we present the effect of UV-C irradiation on the structure and function of pro-apoptotic Bid-FL and anti-apoptotic Bcl-xlΔC proteins. Using a variety of biophysical tools, we show that, following UV-C irradiation, the structures of Bcl-xlΔC and Bid-FL are irreversibly altered. Bcl-xLΔC is found to be more sensitive to UV stress than Bid-FL Interestingly, UV-C exposure shows dramatic chemical shift perturbations in consequence of dramatic structural perturbations (α-helix to β-sheet) in the BH3- binding region, a crucial segment of Bcl-xlΔC. Furter it has been shown that UV-exposed Bcl-xlΔC has reduced efficacy of its interactions with pro-apoptotic tBid., (© 2023 Wiley-VCH GmbH.)

Growing industrialization and unchecked release of industrial waste, including heavy metals have resulted in disastrous effects on environment. Considering the problem of heavy metal pollution, the present research was designed to study the bioremediation of chromium, a highly toxic and prominent heavy metal pollutant by Acinetobacter junii strain b2w isolated from the Mithi river, Mumbai, India. The bacterial isolate could grow without affecting its growth kinetics up to a concentration of 200 ppm of chromium and showed resistance towards 400 ppm of chromium. It was able to bioremediate 83.06% of total chromium and reduces 98.24% of Cr 6+ to C 3+ at a concentration of 10 ppm of chromium. The bacterial isolate could grow well at a wide pH range from 5 to 9, salinity of up to 3.5% and could also tolerate heavy metals such as Cd, Zn, As, Hg, Pb and Cu. Thus, indicating its possible on-ground applicability for bioremediation of chromium. Acinetobacter junii bioaccumulate chromium without disrupting the cell integrity and biosorption. However, chromium alters the functional groups on bacterial cell surface and led to decrease in sulfate-containing molecules. Further, the protein expression study has revealed that Cr significantly up-regulates proteins broadly classified under envelope stress responses, oxidative stress responses, energy metabolism and quorum sensing and growth regulator. The possible mechanisms of Cr detoxification in Acinetobacter junii strain b2w could be reduction, bioaccumulation and efflux along with neutralization of oxidative stress generated by Cr. Thus, based on bacterial bioremediation potential and its molecular response, it can be proposed that the isolated Acinetobacter junii has potential applicability for chromium bioremediation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Bhupendra Pushkar reports financial support was provided by Ramniklal S. Gosalia & Co., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Despite advances in diagnostic, therapeutic and preventive strategies for HIV, pulmonary diseases continue to be the major cause of morbidity and mortality in infants and children infected with HIV. With effective programs to prevent perinatal HIV-1 transmission to early diagnosis in infants, we have seen a substantial decline in paediatric HIV incidence. Early initiation of Highly Active Anti-Retroviral Therapy (HAART) in all HIV infected children coupled with consistent use of Pneumocystis prophylaxis in all HIV exposed/infected children under 5 years of age has considerably reduced associated infections overall and respiratory infections in particular. In developing countries already burdened with poverty, malnutrition, suboptimal immunization coverage and limited access to health care and treatment, acute and chronic HIV-associated respiratory disease remain a major cause for concern. Prevention of severe respiratory infections in advanced HIV disease among children consists mostly of rapid and optimal HAART initiation & continuation, preventing severe TB disease with BCG and TB preventive treatment, preventing Pneumocystis jirovecii pneumonia with cotrimoxazole prophylaxis and administering age-appropriate vaccinations and catch-up vaccines as per National Immunization schedule., Competing Interests: Conflicts of interest The author has none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

The past few decades have seen a rise in research on vertebrate cilia and ciliopathy, with interesting collaborations between basic and clinical scientists. This work includes studies on ciliary architecture, composition, evolution, and organelle generation and its biological role. The human body has cells that harbour any of the following four types of cilia: 9+0 motile, 9+0 immotile, 9+2 motile, and 9+2 immotile. Depending on the type, cilia play an important role in cell/fluid movement, mating, sensory perception, and development. Defects in cilia are associated with a wide range of human diseases afflicting the brain, heart, kidneys, respiratory tract, and reproductive system. These are commonly known as ciliopathies and affect millions of people worldwide. Due to their complex genetic etiology, diagnosis and therapy have remained elusive. Although model organisms like Chlamydomonas reinhardtii have been a useful source for ciliary research, reports of a fascinating and rewarding translation of this research into mammalian systems, especially humans, are seen. The current review peeks into one of the complex features of this organelle, namely its birth, the common denominators across the formation of both 9+0 and 9+2 ciliary types, the molecules involved in ciliogenesis, and the steps that go towards regulating their assembly and disassembly.

Background: Dry powder inhaler is a popular approach to pulmonary drug delivery to treat tuberculosis. Spray dried Nanoparticles using lactose carrier is extensively used for pulmonary drug delivery. Though lactose nanoparticles show deep lung deposition, they fail to uniformly disperse nanoparticles in its original form in alveoli. Rifampicin is one of the first line drugs in tuberculosis treatment. Lung targeted drug delivery system is an approach to reduce dose related side effects of rifampicin. Inhalable nanoparticles also help to target alveolar macrophages, thus improving treatment efficiency., Methodology: This study focuses on rifampicin nanosuspension formulation and optimization using nano-precipitation method followed by characterizing effervescent DPI of rifampicin nanoparticles with effervescent pair (citric acid and sodium bicarbonate). Preliminary studies showed suitability of 4:5 solvent: antisolvent ratio and lecithin (1%) as stabilizer. The drug and stabilizer concentration in nanoparticles was successfully optimized using 3 ∗ 2 factorial design using DESIGN EXPERT software. The rifampicin nanoparticles were further converted to spray dried powder using effervescent carrier., Result: The effervescent pair formulation was monodisperse and had a particle size of 1.5 microns (polydispersity index 0.289), thus showing better redispersibility than lactose nanoparticles. The mass median aerodynamic diameter and fine particle diameter of both spray dried formulations were similar and suitable for deep lung deposition., Conclusion: These findings are suggestive that effervescent technique can be successfully employed to improve redispersibility of rifampicin nanoparticles., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2022 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Expression of affinity-tagged recombinant proteins for crystallography, protein-protein interaction, antibody generation, therapeutic applications, etc. mandates the generation of high-yield soluble proteins. Although recent developments suggest the use of yeast, insect, and mammalian cell lines as protein expression platforms, Escherichia coli is still the most popular, due mainly to its ease of growth, feasibility in genetic manipulation and economy. However, some proteins have a spontaneous tendency to form inclusion bodies (IBs) when over-expressed in bacterial expression systems such as E. coli, thus posing a challenge in purification and yield. At times, small peptides undergo degradation during protein production and hence using suitable tags could circumvent the problem. Although several independent techniques have been used to solubilize IBs, these cannot always be applied in a generic sense. Although tagging a GST moiety is known to enhance the solubility of fusion proteins in E. coli, resulting in yields of 10-50 mg/L of the culture, the inherent nature of the protein sequence at times could lead to the formation of IBs. We have been working on a Myc Binding Protein-1 orthologue, viz. Flagellar Associated Protein 174 (FAP174) from the axoneme of Chlamydomonas reinhardtii that binds to an A-Kinase Anchoring Protein 240 (AKAP240) which has been annotated as Flagellar Associated Protein 65 (FAP65). Using an in-silico approach, we have identified two amphipathic helices on FAP65 (CrFAP65AH1 and CrFAP65AH2) that are predicted to bind to FAP174. To test this prediction, we have cloned the GST-tagged peptides, and overexpressed them in E. coli that have resulted in insoluble IBs. The yields of these over-expressed recombinant proteins dropped considerably due to IB formation, indicating aggregation. An integrated approach has been used to solubilize four highly hydrophobic polypeptides, viz. two amphipathic helices and the respective proline variants of FAP65. For solubilizing these polypeptides, variables such as non-denaturing detergents (IGEPAL CA-630), changing the ionic strength of the cell lysis and solubilization buffer, addition of BugBuster ® , diluting the cell lysate and sonication were introduced. Our statistically viable results yielded highly soluble and functional polypeptides, indiscreet secondary structures, and a yield of ~ 20 mg/L of the E. coli culture. Our combinatorial strategy using chemical and physical methods to solubilize IBs could prove useful for hydrophobic peptides and proteins with amphipathic helices., (© 2022. The Author(s).)

We report the controlled growth of biologically active compounds: gold nanoparticles (AuNPs) in various shapes, including their green synthesis, characterization, and studies of their applications towards biological, degradation and recycling. Using spectroscopic methods, studies on responsive binding mechanisms of AuNPs with biopolymers herring sperm deoxyribonucleic acid (hsDNA), bovine serum albumin (BSA), dyes degradation study, and exquisitely gold separation studies/recovery from nanowaste, COVID-19 testing kits, and pregnancy testing kits are discussed. The sensing ability of the AuNPs with biopolymers was investigated via various analytical techniques. The rate of degradation of various dyes in the presence and absence of AuNPs was studied by deploying stirring, IR, solar, and UV-Vis methods. AuNPs were found to be the most active cytotoxic agent against human breast cancer cell lines such as MCF-7 and MDAMB-468. Furthermore, an economical process for the recovery of gold traces from nanowaste, COVID-19 detection kits, and pregnancy testing kits was developed using inexpensive and eco-friendly α-cyclodextrin sugar. This method was found to be easy and safest in comparison with the universally accepted cyanidation process. In the future, small gold jewelry makers and related industries would benefit from the proposed gold-recycling process and it might contribute to their socio-economic growth. The methodologies proposed are also beneficial for trace-level forensic investigation.

About 50% of the diabetic patients worldwide suffer from Diabetic peripheral neuropathy (DPN) which is characterized by chronic pain and loss of sensation, frequent foot ulcerations, and risk for amputation. Numerous factors like hyperglycemia, oxidative stress (OS), impaired glucose signaling, inflammatory responses, neuronal cell death are known to be the various mechanisms underlying DACD and DPN. Development of tolerance, insufficient and inadequate relief and potential toxicity of classical antinociceptives still remains a challenge in the clinical setting. Therefore, there is an emerging need for novel treatments which are both without any potential side effects as well as which focus more on the pathophysiological mechanisms underlying the disease. Also, sirtuins are known to deacetylate Nrf2 and contribute to its action of reducing ROS by generation of anti-oxidant enzymes. Therefore, targeting sirtuins could be a favourable therapeutic strategy to treat diabetic neuropathy by reducing ROS and thereby alleviating OS in DPN. In the present review, we outline the potential use of SIRT1 activators as therapeutic alternatives in treating DPN. We have tried to highlight how sirtuins are interlinked with Nrf2 and NF-κB and put forth how SIRT activators could serve as potential therapy for DPN., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)