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Background: There is limited evidence on whether active case finding (ACF) among marginalised and vulnerable populations mitigates the financial burden during tuberculosis (TB) diagnosis. Objectives: To determine the effect of ACF among marginalised and vulnerable populations on prevalence and inequity of catastrophic costs due to TB diagnosis among TB-affected households when compared with passive case finding (PCF). Methods: In 18 randomly sampled ACF districts in India, during March 2016 to February 2017, we enrolled all new sputum-smear-positive TB patients detected through ACF and an equal number of randomly selected patients detected through PCF. Direct (medical and non-medical) and indirect costs due to TB diagnosis were collected through patient interviews at their residence. We defined costs due to TB diagnosis as ‘catastrophic’ if the total costs (direct and indirect) due to TB diagnosis exceeded 20% of annual pre-TB household income. We used concentration curves and indices to assess the extent of inequity. Results: When compared with patients detected through PCF (n = 231), ACF patients (n = 234) incurred lower median total costs (US$ 4.6 and 20.4, p

Background: In 2007, a field observation from India reported 11% misclassification among ‘new’ patients registered under the revised national tuberculosis (TB) control programme. Ten years down the line, it is important to know what proportion of newly registered patients has a past history of TB treatment for at least one month (henceforth called ‘misclassification’). Methods: A study was conducted among new smear-positive pulmonary TB patients registered between March 2016 and February 2017 in 18 randomly selected districts to determine the effectiveness of an active case-finding strategy in marginalised and vulnerable populations. We included all patients detected through active case-finding. An equal number of randomly selected patients registered through passive case-finding from marginalised and vulnerable populations in the same districts were included. Before enrolment, we enquired about any history of previous TB treatment through interviews. Results: Of 629 patients, we interviewed 521, of whom, 11% (n=56) had past history of TB treatment (public or private) for at least a month: 13% (34/268) among the active case-finding group and 9% (22/253) among the passive case-finding group (p=0.18). No factors were found to be significantly associated with misclassification. Conclusion: Around one in every ten patients registered as ‘new’ had previous history of TB treatment. Corrective measures need to be implemented, followed by monitoring of any change in the proportion of ‘previously treated’ patients among all registered patients treated under the programme at national level.

Background: In 2007, a field observation from India reported 11% misclassification among ‘new’ patients registered under the revised national tuberculosis (TB) control programme. Ten years down the line, it is important to know what proportion of newly registered patients has a past history of TB treatment. Methods: A study was conducted among new smear-positive pulmonary TB patients registered between March 2016 and February 2017 in 18 randomly selected districts to determine the effectiveness of an active case-finding strategy in marginalised and vulnerable populations. We included all patients detected through active case-finding. An equal number of randomly selected patients registered through passive case-finding from marginalised and vulnerable populations in the same districts were included. Before enrolment, we enquired about any history of previous TB treatment through interviews. Results: Of 629 patients, we interviewed 521, of whom, 11% (n=56) had past history of TB treatment (public or private) for at least a month: 13% (34/268) among the active case-finding group and 9% (22/253) among the passive case-finding group (p=0.18). No factors were found to be significantly associated with misclassification. Conclusion: Around one in every ten patients registered as ‘new’ had previous history of TB treatment. Corrective measures need to be implemented, followed by monitoring of any change in the proportion of ‘previously treated’ patients among all registered patients treated under the programme at national level.

BackgroundAxshya SAMVAD is an active tuberculosis (TB) case finding (ACF) strategy under project Axshya (Axshya meaning 'free of TB' and SAMVAD meaning 'conversation') among marginalized and vulnerable populations in 285 districts of India.ObjectivesTo compare patient characteristics, health seeking, delays in diagnosis and treatment initiation among new sputum smear positive TB patients detected through ACF and passive case finding (PCF) under the national TB programme in marginalized and vulnerable populations between March 2016 and February 2017.MethodsThis observational analytic study was conducted in 18 randomly sampled Axshya districts. We enrolled all TB patients detected through ACF and an equal number of randomly selected patients detected through PCF in the same settings. Data on patient characteristics, health seeking and delays were collected through record review and patient interviews (at their residence). Delays included patient level delay (from eligibility for sputum examination to first contact with any health care provider (HCP)), health system level diagnosis delay (from contact with first HCP to TB diagnosis) and treatment initiation delays (from diagnosis to treatment initiation). Total delay was the sum of patient level, health system level diagnosis delay and treatment initiation delays.ResultsWe included 234 ACF-diagnosed and 231 PCF-diagnosed patients. When compared to PCF, ACF patients were relatively older (≥65 years, 14% versus 8%, p = 0.041), had no formal education (57% versus 36%, pConclusionAxshya SAMVAD linked the most impoverished communities to TB care and resulted in reduction of health system level diagnosis delay.

Most of the triple negative phenotype or basal-like molecular subtypes of breast cancers are associated with aggressive clinical behaviour and show poor disease prognosis. Current treatment options are constrained, emphasizing the need for novel combinatorial therapies for this particular tumor subtype. Our group has demonstrated that functionally active p21 activated kinase 1 (PAK1) exhibits significantly higher expression levels in clinical triple negative breast cancer (TNBC) samples compared to other subtypes, as well as adjacent normal tissues. Low PAK1 expression in TNBC was significantly linked to better prognosis, with improved overall survival (OS, p=0.00236) and relapse-free survival (RFS, p=0.0314), as shown by GOBO analysis. To confirm the role of PAK1 as a therapeutic target and to discover novel synergistic chemotherapy drug combinations, we conducted a drug combination screen using triple negative breast cancer cell lines and a mouse metastatic tumor cell line. We identified the combined inhibition of PAK1 inhibitor, NVS-PAK1 with doxorubicin/paclitaxel/methotrexate as a synergistic novel therapeutic approach for treating metastatic TNBC to improve overall survival. This study also indicated a reduction in the effective dosage of the chemotherapeutic drug when combined with NVS-PAK1. Our study demonstrates that combining NVS-PAK1 with each of the chemotherapeutic drugs' doxorubicin, paclitaxel, and methotrexate resulted in decreased colony formation, reduced wound healing capability, and diminished migratory and invasive potential in both TNBC cell lines and 4T1 in vitro. These findings were further validated in orthotopic mouse mammary tumors, confirming that simultaneous PAK1 inhibition alongside chemotherapy significantly enhanced anti-tumor efficacy and reduced metastasis.

Hepatocyte nuclear factor 4-alpha (HNF4α), a well-preserved member of the nuclear receptor superfamily of transcription factors, is found in the liver. It is recognized as a central controller of gene expression specific to the liver and plays a key role in preserving the liver's homeostasis. Irregular expression of HNF4α is increasingly recognized as a crucial factor in the proliferation, cell death, invasiveness, loss of specialized functions, and metastasis of cancer cells. An increasing number of studies are pointing to abnormal HNF4α expression as a key component of cancer cell invasion, apoptosis, proliferation, dedifferentiation, and metastasis. Understanding HNF4α's intricate involvement in liver carcinogenesis provides a promising avenue for therapeutic intervention. This chapter attempts to shed light on the diverse aspects of HNF4's role in liver carcinogenesis and demonstrate how this knowledge can be harnessed for approaches to prevent and treat liver cancer. This comprehensive chapter will offer an elaborate perspective on HNF4's function in liver cancer, delineating its molecular mechanisms that aid in the emergence of liver cancer. Furthermore, it will highlight the potential to help create more effective and precisely targeted therapeutic strategies, rekindling fresh optimism in the fight against this formidable condition., (Copyright © 2025. Published by Elsevier Inc.)

Parkinson's disease (PD) is a complex neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the substantia nigra. While current treatments primarily manage symptoms, there is increasing interest in alternative approaches, particularly the use of phytochemicals from medicinal plants. These natural compounds have demonstrated promising neuroprotective potential in preclinical studies by targeting key pathological mechanisms such as oxidative stress, neuroinflammation, and protein aggregation. However, the clinical translation of these phytochemicals is limited due to a lack of robust clinical trials evaluating their safety, efficacy, and pharmacokinetics. This review provides a comprehensive overview of the neuroprotective potential of phytochemicals in PD management, examining the mechanisms underlying PD pathogenesis and emphasizing neuroprotection. It explores the historical and current research on medicinal plants like Mucuna pruriens, Curcuma longa, and Ginkgo biloba, and discusses the challenges in clinical translation, including ethical and practical considerations and the integration with conventional therapies. It further underscores the need for future research to elucidate mechanisms of action, optimize drug delivery, and conduct rigorous clinical trials to establish the safety and efficacy of phytochemicals, aiming to shape future neuroprotective strategies and develop more effective, personalized treatments for PD., Competing Interests: Compliance with Ethical Standards Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Endometrial cancer is the sixth most common gynecologic cancer, and has been reported as a malignancy arising due to the idiopathic effects of certain anticancer agents. Tamoxifen is the drug of choice in ER-positive breast cancer, and several studies have shown better disease-free survival in these patients. However, the long-term usage of tamoxifen has been associated with resistance and risk for endometrial malignancy. A direct mechanistic basis for tamoxifen-induced endometrial tumorigenesis is still unclear. Hyperactivation of PAK1 in endometrial cancer correlates with poor overall survival. The present study demonstrates that tamoxifen treatment induces nuclear localization of PAK1 in endometrial carcinoma cells. This nuclear transit is mediated through JAK2 phosphorylation of PAK1 and binding of β-PIX. In addition, a computational approach involving molecular modeling and simulation of phosphorylated and unphosphorylated forms of PAK1 was used to elucidate the dynamics of nuclear localization. Thus, PAK1 phosphorylation by JAK2 is a prerequisite for its nuclear localization and its tumorigenic effects on endometrial cancer cells., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

Research Question: What are the specific genetic alterations and associated network in endometriotic cells responsible for the disease pathogenesis?, Design: Case control experimental study involving 45 women with endometriosis who underwent laparoscopic surgery (case) and 45 normal samples from women undergoing total abdominal hysterectomy (control). The endometrial samples were subjected to whole exome sequencing (WES) of endometriotic tissue and copy number variation analysis. Validation of gene hits were obtained from WES using polymerase chain reaction techniques, immunological techniques, in-silico tools and transgenic cell line models., Results: Germline heterozygous deletion of mRNA editing enzyme subunit APOBEC3B was identified in about 96% of endometriosis samples. The presence of germline deletion was confirmed with blood, endometrium and normal ovary samples obtained from the same patient. APOBEC3B deletions resulted in a hybrid protein that activates A1CF. APOBEC3B deletion can be a major cause of changes in the endometriotic microenvironment, and contributes to the pathogenesis and manifestation of the disease. The effect of APOBEC3B deletion was proved by in-vitro experiments in a cell line model, which displayed endometriosis-like characteristics. APOBEC3B germline deletion plays a major role in the pathogenesis of endometriosis, which is evident by the activation of A1CF, an increase in epithelial to mesenchymal transition, cellular proliferation, inflammation markers and a decrease in apoptosis markers., Conclusion: The deleterious effects caused by APOBEC3B deletion in endometriosis were identified and confirmed. These results might provide a base for identifying the complete pathogenetic mechanism of endometriosis, thereby moving a step closer to better diagnosis and treatment options., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Type 2 Diabetes Mellitus (T2DM) presents a substantial health concern on a global scale, driving the search for innovative therapeutic strategies. Phytochemicals from medicinal plants, particularly Ocimum tenuiflorum (Holy Basil), have garnered attention for their potential in T2DM management. The increased focus on plant-based treatments stems from their perceived safety profile, lower risk of adverse effects, and the diverse range of bioactive molecules they offer, which can target multiple pathways involved in T2DM. Computational techniques explored the binding interactions between O. tenuiflorum phytochemicals and Human Omentin-1, a potential T2DM target. ADMET evaluation and targeted docking identified lead compounds: Luteolin (-4.84 kcal/mol), Madecassic acid (-4.12 kcal/mol), Ursolic acid (-5.91 kcal/mol), Stenocereol (-5.59 kcal/mol), and Apigenin (-4.64 kcal/mol), to have a better binding affinity to target protein compared to the control drug, Metformin (-2.01 kcal/mol). Subsequent molecular dynamics simulations evaluated the stability of Stenocereol, Luteolin, and Metformin complexes for 200 nanoseconds, analysing RMSD, RMSF, RG, SASA, PCA, FEL, and MM-PBSA parameters. Results indicated Stenocereol's strong binding affinity with Omentin-1, suggesting its potential as a potent therapeutic agent for T2DM management. These findings lay the groundwork for further experimental validation and drug discovery endeavours., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Triple-negative breast carcinoma (TNBC) is one of the most challenging subtypes of breast carcinoma and it has very limited therapeutic options as it is highly aggressive. The prognostic biomarkers are crucial for early diagnosis of the tumor, it also helps in anticipating the trajectory of the illness and optimizing the therapy options. Several therapeutic biomarkers are being used. Among them, the next-generation biomarkers that include Circulating tumor (ct) DNA, glycogen, lipid, and exosome biomarkers provide intriguing opportunities for enhancing the prognosis of TNBC. Lipid and glycogen biomarkers serve as essential details on the development of the tumor along with the efficacy of the treatment, as it exhibits metabolic alteration linked to TNBC. Several types of biomarkers have predictive abilities in TNBC. Elevated levels are associated with worse outcomes. ctDNA being a noninvasive biomarker reveals the genetic composition of the tumor, as well as helps to monitor the progression of the disease. Traditional therapies are ineffective in TNBC due to a lack of receptors, targeted drug delivery provides a tailored approach to overcome drug resistance and site-specific action by minimizing the side effects in TNBC treatment. This enhances therapeutic outcomes against the aggressive nature of breast cancer. This paper includes all the recent biomarkers which has been researched so far in TNBC and the state of art for TNBC which is explored., Competing Interests: Declaration of Competing Interest No conflict, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Long-term metabolic disease type 2 diabetes mellitus (T2DM) is distinguished by elevated blood glucose, insulin resistance, and drought of insulin with dyslipidemia. Oral hypoglycemic agents lower blood glucose levels as well as prevent both short-term and long-term complications such as micro/macrovascular atherosclerosis, chronic kidney diseases, and chronic heart disease. This study aims to compare the effect of glimepiride versus teneligliptin in combination with metformin in T2DM patients attending a tertiary care hospital., Materials and Methods: This prospective, randomized, open-label study was initiated in a tertiary care hospital after obtaining IEC approval. Written informed consent was obtained. The sample size was calculated using "Statistics and sample size software." Ninety-seven patients satisfying the inclusion criteria were assigned to two groups using simple randomization with allocation 1:1. Group A received metformin + glimepiride while Group B received metformin + teneligliptin for 12 weeks. Fasting blood sugar (FBS), postprandial blood sugar (PPBS), glycated hemoglobin (HbA1c), and lipid profile were recorded at the baseline and at the end of 12 weeks. This study was conducted for 1 year. Data were analyzed using SPSS version 23.0 software., Results: Out of 97 participants (Group A: 48 and Group B: 49), Group A showed a higher reduction in FBS (48.18 ± 9.64) whereas Group B showed 72.53 ± 5.01, 1.74 ± 0.42 of change in PPBS and HbA1c after 12 weeks., Conclusion: The study found that combining metformin with teneligliptin was better tolerated and improved glycemic control and lipid profile compared to metformin plus glimepiride., (Copyright © 2024 Indian Journal of Pharmacology.)

Alternanthera sessilis (AS) leaf extract was used to synthesize zinc oxide nanoparticles (ZnO NPs). Bioanalytical characterization techniques such as X-ray diffraction (XRD) and field emission scanning electron microscope (FESEM) confirmed the formation of crystalline ZnO NPs with average sizes of 40 nm. The AS-ZnO NPs antimicrobial activity was analyzed under dark (D) and white light (WL) conditions. The improved antimicrobial activity was observed against Escherichia coli, Staphylococcus aureus and Bacillus subtilis at the minimal inhibitory concentration (MIC) of 125 and 62.5 µg/mL under WL than the D at 125 and 250 µg/mL for E. coli, B. subtilis, and Pseudomonas aeruginosa, respectively. In contrast, the growth of P. aeruginosa and S. aureus was not completely inhibited until 1 mg/mL AS-ZnO NPs under WL and D. Similarly, AS-ZnO NPs displayed a weaker inhibitory effect against carbapenem-sensitive P. aeruginosa (CSPA) and carbapenem-resistant P. aeruginosa (CRPA) strains of PAC023, PAC041 and PAC032, PAC045 under D. Interestingly, the distinct inhibitory effect was recorded against CSPA PAC041 and CRPA PAC032 in which the bacteria growth was inhibited 99.9% at 250, 500 µg/mL under WL. The cytotoxicity results suggested AS-ZnO NPs demonstrated higher toxicity to MCF-7 breast cancer cells than the RAW264.7 macrophage cells. Further, AS-ZnO NPs exhibited higher catalytic potential against tetracycline hydrochloride (TC-H) degradation at 65.6% and 60.8% under WL than the dark at 59.35% and 48.6% within 120 min. Therefore, AS-ZnO NPs can be used to design a photo-improved antimicrobial formulation and environmental catalyst for removing TC-H from wastewater., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study used Morinda citrifolia leaf (MCL) extract to synthesise Zinc oxide nanoparticles (ZnO NPs) and ZnO decorated silver nanocomposites (ZnO/Ag NCs). The synthesized nanomaterials structural morphology and crystallinity were characterized using a Field emission scanning electron microscope (FESEM) and X-ray diffraction (XRD) analysis. The antimicrobial activity of ZnO NPs and ZnO/Ag NCs was evaluated using human nosocomial bacterial pathogens. The highest antimicrobial activity was recorded for ZnO/Ag NCs at the minimum inhibitory concentration (MIC) at 80 and 100 μg/mL for Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis, Staphylococcus aureus than ZnO NPs at the MIC of 120 and 140 μg/mL for Bacillus subtilis and Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus. Furthermore, ROS detection, viability assay and bacterial membrane integrity analysis of ZnO/Ag NCs treated P. aeruginosa and S. aureus revealed the fundamental bactericidal mechanism involving cell wall, cell membrane interaction and release of cytoplasmic contents. In addition, ZnO/Ag NCs and ZnO NPs showed higher toxicity towards A549 lung cancer cells than the non-cancerous RAW264 macrophage cells, with IC 50 of 242 and 398 µg/mL respectively, compared to IC 50 of 402 and 494 µg/mL for the macrophage cells. These results suggest that the ZnO/Ag NCs can be effectively used to develop antimicrobial and anticancer materials., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Almost 70% of clinically used antineoplastic drugs are originated from natural products such as plants, marine organism, and microorganisms and some of them are also structurally modified natural products. The naturally occurring drugs may specifically act as inducers of selective cytotoxicity, anti-metastatic, anti-mutagenic, anti-angiogenesis, antioxidant accelerators, apoptosis inducers, autophagy inducers, and cell cycle inhibitors in cancer therapy. Precisely, several reports have demonstrated the involvement of naturally occurring anti-breast cancer drugs in regulating the expression of oncogenic and tumor suppressors associated with carcinogen metabolism and signaling pathways. Anticancer therapies based on nanotechnology have the potential to improve patient outcomes through targeted therapy, improved drug delivery, and combination therapies. This paper has reviewed the current treatment for breast cancer and the potential disadvantages of those therapies, besides the various mechanism used by naturally occurring phytochemicals to induce apoptosis in different types of breast cancer. Along with this, the contribution of nanotechnology in improving the effectiveness of anticancer drugs was also reviewed. With the development of sciences and technologies, phytochemicals derived from natural products are continuously discovered; however, the search for novel natural products as chemoprevention drugs is still ongoing, especially for the advanced stage of breast cancer. Continued research and development in this field hold great promise for advancing cancer care and improving patient outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neural tissue engineering is a sub-field of tissue engineering that develops neural tissue. Damaged central and peripheral nervous tissue can be fabricated with a suitable scaffold printed with biomaterials. These scaffolds promote cell growth, development, and migration, yet they vary according to the biomaterial and scaffold printing technique, which determine the physical and biochemical properties. The physical and biochemical properties of scaffolds stimulate diverse signalling pathways, such as Wnt, NOTCH, Hedgehog, and ion channels- mediated pathways to promote neuron migration, elongation and migration. However, neurotransmitters like dopamine, acetylcholine, gamma amino butyric acid, and other signalling molecules are critical in neural tissue engineering to tissue fabrication. Thus, this review focuses on neural tissue regeneration with a tissue engineering approach highlighting the signalling pathways. Further, it explores the interaction of the scaffolds with the signalling pathways for generating neural tissue., 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 © 2024 Elsevier Inc. All rights reserved.)

Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor-2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN-LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p < 0.0001), respectively. Similarly, LIV1 levels were elevated in secondary tumors than primary & in patient samples postchemotherapy as compared to naïve. In the TNBC cohort, using automated method, cell morphology parameters were computed and analysis showed LIV1 levels were elevated in grade 3 TNBC samples presenting with altered cell morphology parameters namely cell size, cell perimeter, & nucleus size. Thus indicating LIV1 expressing TNBC samples portrayed an aggressive phenotype. Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+ LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies., (© 2024 Wiley Periodicals LLC.)

Polycyclic Aromatic Hydrocarbons (PAHs) profoundly impact public and environmental health. Gaining a comprehensive understanding of their intricate functions, exposure pathways, and potential health implications is imperative to implement remedial strategies and legislation effectively. This review seeks to explore PAH mobility, direct exposure pathways, and cutting-edge bioremediation technologies essential for combating the pervasive contamination of environments by PAHs, thereby expanding our foundational knowledge. PAHs, characterised by their toxicity and possession of two or more aromatic rings, exhibit diverse configurations. Their lipophilicity and remarkable persistence contribute to their widespread prevalence as hazardous environmental contaminants and byproducts. Primary sources of PAHs include contaminated food, water, and soil, which enter the human body through inhalation, ingestion, and dermal exposure. While short-term consequences encompass eye irritation, nausea, and vomiting, long-term exposure poses risks of kidney and liver damage, difficulty breathing, and asthma-like symptoms. Notably, cities with elevated PAH levels may witness exacerbation of bronchial asthma and chronic obstructive pulmonary disease (COPD). Bioremediation techniques utilising microorganisms emerge as a promising avenue to mitigate PAH-related health risks by facilitating the breakdown of these compounds in polluted environments. Furthermore, this review delves into the global concern of antimicrobial resistance associated with PAHs, highlighting its implications. The environmental effects and applications of genetically altered microbes in addressing this challenge warrant further exploration, emphasising the dynamic nature of ongoing research in this field., 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 © 2024 Elsevier Ltd. All rights reserved.)

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus (DM) that poses a serious risk as it can lead to end-stage renal disease (ESRD). DKD is linked to changes in the diversity, composition, and functionality of the microbiota present in the gastrointestinal tract. The interplay between the gut microbiota and the host organism is primarily facilitated by metabolites generated by microbial metabolic processes from both dietary substrates and endogenous host compounds. The production of numerous metabolites by the gut microbiota is a crucial factor in the pathogenesis of DKD. However, a comprehensive understanding of the precise mechanisms by which gut microbiota and its metabolites contribute to the onset and progression of DKD remains incomplete. This review will provide a summary of the current scenario of metabolites in DKD and the impact of these metabolites on DKD progression. We will discuss in detail the primary and gut-derived metabolites in DKD, and the mechanisms of the metabolites involved in DKD progression. Further, we will address the importance of metabolomics in helping identify potential DKD markers. Furthermore, the possible therapeutic interventions and research gaps will be highlighted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Benzopyrene (BaP) stands as a potent polycyclic aromatic hydrocarbon (PAH) molecule, boasting five fused aromatic rings, making its way into the human food chain through soil contamination. The persistent environmental presence of PAHs in soil, attributed to industrial exposure, is primarily due to their low molecular weight and hydrophobic nature. To preemptively address the entry of BaP into the food chain, the application of nanocomposites was identified as an effective remediation strategy. Post-synthesis, comprehensive characterization tests employing techniques such as UV-DRS, XRD, SEM-EDX, FTIR, and DLS unveiled the distinctive features of the g-C 3 N 4 -SnS nanocomposites. These nanocomposites exhibited spherical shapes embedded on layers of nanosheets, boasting particle diameters measuring 88.9 nm. Subsequent tests were conducted to assess the efficacy of eliminating benzopyrene from a combination of PAH molecules and g-C 3 N 4 -SnS nanocomposites. Varied parameters, including PAH concentration, adsorbent dosage, and suspension pH, were systematically explored. The optimized conditions for the efficient removal of BaP utilizing the g-C 3 N 4 -SnS nanocomposite involved 2 μg/mL of benzopyrene, 10 μg/mL of the nanocomposite, and a pH of 5, considering UV light as the irradiation source. The investigation into the mechanism governing BaP elimination closely aligned with batch adsorption results involved a thorough exploration of adsorption kinetics and isotherms. Photocatalytic degradation of benzopyrene was achieved, reaching a maximum of 86 % in 4 h and 36 % in 2 h, with g-C 3 N 4 -SnS nanocomposite acting as the catalyst. Further validation through HPLC data confirmed the successful removal of BaP from the soil matrix., 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 © 2024 Elsevier Ltd. All rights reserved.)

Diabetes constitutes a significant global public health challenge that is rapidly reaching epidemic proportions. Among the non-communicable diseases, the incidence of diabetes is rising at an alarming rate. The International Diabetes Federation has documented a 9.09% prevalence of diabetes among individuals aged between 20 and 79 years. The interplay of gonadal hormones and gender differences is critical in regulating insulin sensitivity and glucose tolerance, and this dynamic is particularly crucial because of the escalating incidence of diabetes. Variations in insulin sensitivity are observed across genders, levels of adiposity, and age groups. Both estrogen and testosterone are seen to influence glucose metabolism and insulin sensitivity. This chapter surveys the present knowledge of sex differences, sex hormones, and chromosomes on insulin imbalance and diabetes development. It further highlights the influence of metabolic traits in diabetes and changes in sex hormones during diabetic pregnancy. Notably, even stressful lifestyles have been acknowledged to induce hormonal imbalances. Furthermore, it discusses the potential of hormonal therapy to help stabilize sex hormones in diabetic individuals and focuses on the most recent research investigating the correlation between sex hormones and diabetes., (Copyright © 2024. Published by Elsevier Inc.)

Type 2 diabetes mellitus (T2DM) is a worldwide health problem that has raised major concerns to the public health community. This chronic condition typically results from the cell's inability to respond to normal insulin levels. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the primary incretin hormones secreted from the intestinal tract. While clinical research has extensively explored the therapeutic potential of GLP-1R in addressing various T2DM-related abnormalities, the possibility of GIPR playing an important role in T2DM treatment is still under investigation. Evidence suggests that GIP is involved in the pathophysiology of T2DM. This chapter focuses on examining the role of GIP as a therapeutic molecule in combating T2DM, comparing the past, present, and future scenarios. Our goal is to delve into how GIP may impact pancreatic β-cell function, adipose tissue uptake, and lipid metabolism. Furthermore, we will elucidate the mechanistic functions of GIP and its receptors in relation to other clinical conditions like cardiovascular diseases, non-alcoholic fatty liver diseases, neurodegenerative diseases, and renal disorders. Additionally, this chapter will shed light on the latest advancements in pharmacological management for T2DM, highlighting potential structural modifications of GIP and the repurposing of drugs, while also addressing the challenges involved in bringing GIP-based treatments into clinical practice., (Copyright © 2024. Published by Elsevier Inc.)

Head and neck squamous cancers are very aggressive tumors often diagnosed in late stages with poor prognosis. HNSCCs are usually treated by a course of radiation (IR) therapy and followed by surgery. These treatment regimens fail to bring a complete response. Molecular signatures in tumors are attributed to this response and an improved understanding of the signaling events could offer new avenues for therapy. Here, we show that P21 activated kinase-1 (PAK1) - an oncogenic signaling serine/threonine kinase, is activated upon exposure to IR and this leads to an accelerated tumorigenic character in HNSCC cells. Our results show that PAK1 is highly expressed in HNSCC cell lines, as compared to normal buccal mucosa cells and when HNSCC cells were exposed to IR, they show activated PAK1 and an aggressive phenotype as determined by in vitro functional assays. PAK1 levels were elevated in HNSCC as compared to adjacent normal oral tissues and our results also show convincing evidence of activated PAK1 in patient tumor samples of post- IR treatment as compared to pre-IR treatment and is associated with poor survival. Pak1 Knockout (KO) clones in HNSCC cells showed that they were more sensitive to IR as compared to wild type (wt) cells. This altered sensitivity to IR was attributed to enhanced DNA damage response modulated by PAK1 in cells. Overall, our results suggest that PAK1 expression in HNSCC could be a critical determinant in IR therapy response and silencing PAK1 is likely to be a treatment modality to improve clinical outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A steadily increasing production volume of nanoparticles reflects their numerous industrial and domestic applications. These economic successes come with the potential adverse effects on natural systems that are associated with their presence in the environment. Biological activities and effects of nanoparticles are affected by their entry method together with their specificities like their size, shape, charge, area, and chemical composition. Particles can be classified as safe or dangerous depending on their specific properties. As both aquatic and terrestrial systems suffer from organic and inorganic contamination, nanoparticles remain a sink for these contaminants. Researching the sources, synthesis, fate, and toxicity of nanoparticles has advanced significantly during the last ten years. We summarise nanoparticle pathways throughout the ecosystem and their interactions with beneficial microorganisms in this research. The prevalence of nanoparticles in the ecosystem causes beneficial microorganisms to become hazardous to their cells, which prevents the synthesis of bioactive molecules from undergoing molecular modifications and diminishes the microbe population. Recently, observed concentrations in the field could support predictions of ambient concentrations based on modeling methodologies. The aim is to illustrate the beneficial and negative effects that nanoparticles have on aqueous and terrestrial ecosystems, as well as the methods utilized to reduce their toxicity., 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.)

Lifestyle modification can lead to numerous health issues closely associated with sleep. Sleep deprivation and disturbances significantly affect inflammation, immunity, neurodegeneration, cognitive depletion, memory impairment, neuroplasticity, and insulin resistance. Sleep significantly impacts brain and memory formation, toxin excretion, hormonal function, metabolism, and motor and cognitive functions. Sleep restriction associated with insulin resistance affects these functions by interfering with the insulin signalling pathway, neurotransmission, inflammatory pathways, and plasticity of neurons. So, in this review, We discuss the evidence that suggests that neurodegeneration occurs via sleep and is associated with insulin resistance, along with the insulin signalling pathways involved in neurodegeneration and neuroplasticity, while exploring the role of hormones in these conditions., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Ovarian cancers are tumors that originate from the different cells of the ovary and account for almost 4% of all the cancers in women globally. More than 30 types of tumors have been identified based on the cellular origins. Epithelial ovarian cancer (EOC) is the most common and lethal type of ovarian cancer which can be further divided into high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous carcinoma. Ovarian carcinogenesis has been long attributed to endometriosis which is a chronic inflammation of the reproductive tract leading to progressive accumulation of mutations. Due to the advent of multi-omics datasets, the consequences of somatic mutations and their role in altered tumor metabolism has been well elucidated. Several oncogenes and tumor suppressor genes have been implicated in the progression of ovarian cancer. In this review, we highlight the genetic alterations undergone by the key oncogenes and tumor suppressor genes responsible for the development of ovarian cancer. We also summarize the role of these oncogenes and tumor suppressor genes and their association with a deregulated network of fatty acid, glycolysis, tricarboxylic acid and amino acid metabolism in ovarian cancers. Identification of genomic and metabolic circuits will be useful in clinical stratification of patients with complex etiologies and in identifying drug targets for personalized therapies against cancer.

Melioidosis, also known as Whitmore's disease, is a potentially fatal infection caused by the Gram-negative bacteria Burkholderia pseudomallei with a mortality rate of 10-50%. The condition is a "glanders-like" illness prevalent in Southeast Asian and Northern Australian regions and can affect humans, animals, and sometimes plants. Melioidosis received the epithet "the great mimicker" owing to its vast spectrum of non-specific clinical manifestations, such as localised abscesses, septicaemia, pneumonia, septic arthritis, osteomyelitis, and encephalomyelitis, which often lead to misdiagnosis and ineffective treatment. To date, antibiotics remain the backbone of melioidosis treatment, which includes intravenous therapy with ceftazidime or meropenem, followed by oral therapy with TMP-SMX or amoxicillin/clavulanic acid and supported by adjunctive treatment. However, bacteria have developed resistance to a series of antibiotics, including clinically significant ones, during treatment. Therefore, phage therapy has gained unprecedented interest and has been proposed as an alternative treatment. Although no effective phage therapy has been published, the findings of experimental phage therapies suggest that the concept could be feasible. This article reviews the benefits and limitations of antibiotics and phage therapy in terms of established regimens, bacterial resistance, host specificity, and biofilm degradation.

Breast cancer is one of the leading causes contributing to the global cancer burden. The triple negative breast cancer (TNBC) molecular subtype accounts for the most aggressive type. Despite progression in therapeutic options and prognosis in breast cancer treatment options, there remains a high rate of distant relapse. With advancements in understanding the role of zinc and zinc carriers in the prognosis and treatment of the disease, the scope of precision treatment/targeted therapy has been expanded. Zinc levels and zinc transporters play a vital role in maintaining cellular homeostasis, tumor surveillance, apoptosis, and immune function. This review focuses on the zinc transporter, LIV1, as an essential target for breast cancer prognosis and emerging treatment options. Previous studies give an insight into the role of LIV1 in fulfilling the most important hallmarks of cancer such as apoptosis, metastasis, invasion, and evading the immune system. Normal tissue expression of LIV1 is limited. Higher expression of LIV1 has been linked to Epithelial-Mesenchymal Transition, histological grade of cancer, and early node metastasis. LIV1 was found to be one of the attractive targets in the therapeutic hunt for TNBCs. TNBCs are an immunogenic breast cancer subtype. As zinc transporters are known to serve as the metabolic gatekeepers of immune cells, this review bridges tumor infiltrating lymphocytes, TNBC and LIV1. In addition, the suitability of LIV1 as an antibody-drug conjugate (Seattle genetics [SGN]-LIV1A) target in TNBC, represents a promising strategy for patients. Early clinical trial results reveal that this novel agent reduces tumor burden by inducing mitotic arrest, immunomodulation, and immunogenic cell death, warranting further investigation of SGN-LIV1A in combination with immuno-oncology agents. Priming the patient's immune response in combination with SGN-LIV1A could eventually change the landscape for the TNBC patient population., (© 2022 Wiley Periodicals LLC.)

Targeting the challenging tumors lacking explicit markers and predictors for chemosensitivity is one of the major impediments of the current cancer armamentarium. Triple-negative breast cancer (TNBC) is an aggressive and challenging molecular subtype of breast cancer, which needs astute strategies to achieve clinical success. The pro-survival B-cell lymphoma 2 (BCL-2) overexpression reported in TNBC plays a central role in deterring apoptosis and is a promising target. Here, we propose three novel BH4 mimetic small molecules, SM396, a covalent binder, and two non-covalent binders, i.e., SM216 and SM949, which show high binding affinity (nM) and selectivity, designed by remodeling the existing BCL-2 chemical space. Our mechanistic studies validate the selectivity of the compounds towards cancerous cells and not on normal cells. A series of functional assays illustrated BCL-2-mediated apoptosis in the tumor cells as a potent anti-cancerous mechanism. Moreover, the compounds exhibited efficacious in vivo activity as single agents in the MDA-MB-231 xenograft model (at nanomolar dosage). Overall, these findings depict SM216, SM396, and SM949 as promising leads, pointing to the clinical translation of these compounds in targeting triple-negative breast cancer.

Aims: High mobility group box (HMGB) family proteins, HMGB1, HMGB2, HMGB3, and HMGB4 are oncogenic. The oncogenic nature of HMGB1 is characterized by its association with autophagy, ROS, and MMP. Since HMGB3 is its paralog, we hypothesized that it might also modulate autophagy, ROS, and MMP. Hence, we targeted HMGB3 using its shRNA or miR-142-3p and assessed the changes in autophagy, ROS, MMP, and tumorigenic properties of human breast cancer cells., Main Methods: Cell viability was assessed by resazurin staining and annexin-V/PI dual staining was used for confirming apoptosis. Colony formation, transwell migration, invasion and luciferase reporter (for miRNA-target validation) assays were also performed. ROS and MMP were detected using DHE and MitoTracker dyes, respectively. A zebrafish xenograft model was used to assess the role of miR-142-3p on in vivo metastatic potential of breast cancer cells., Key Findings: Breast cancer tissues from Indian patients and TCGA samples exhibit overexpression of HMGB3. miR-142-3p binds to 3' UTR of HMGB3, leading to its downregulation that subsequently inhibits colony formation and induces apoptosis involving increased ROS accumulation and decreased MMP, phospho-mTOR and STAT3. Our findings show that HMGB3 is directly involved in the miR-142-3p-mediated disruption of autophagy and induction of apoptotic cell death via modulation of LC3, cleaved PARP and Bcl-xL. In addition, miR-142-3p inhibited migration, invasion and metastatic potential of breast cancer cells., Significance: Our findings highlighted the role of HMGB3, for the first time, in the modulation of autophagy and apoptosis in human breast cancer cells, and these results have therapeutic implications., (Copyright © 2022. Published by Elsevier Inc.)

This study aimed to determine the prevalence of bacterial vaginosis (BV) and aerobic vaginitis (AV) and their associated risk factors among pregnant women from Ethiopia. Also, this study investigated the bacterial pathogens and their antibiotic resistance in AV cases. A total of 422 pregnant women from northern Ethiopia were participated in this study. Socio-demographic and clinical data were recorded. Vaginal swabs were collected and used for wet mount and Gram stain methods to evaluate the AV and BV scores according to the Nugent's and Donder's criteria, respectively. In AV cases the bacterial pathogens and their antibiotic resistance were determined using standard methods. The possible risk factors for AV and BV in pregnant women were investigated. The prevalence rates of BV and AV were 20.1% (85/422) and 8.1% (34/422), respectively. BV was more common in symptomatic vs. asymptomatic people (P < 0.001), and in second trimester vs. first trimester samples (P = 0.042). However, AV was more common in secondary school vs. primary and those who were unable to read and write (P = 0.021) and in housewife women vs. employee (P = 0.013). A total of 44 bacterial strains were isolated from AV cases, of which the coagulase-negative staphylococci (CoNS) (38.6%) and Staphylococcus aureus (29.5%) were the most predominant bacteria, respectively. The highest resistance rate was observed against penicillin (100.0%) in staphylococci, while 86.7% of them were sensitive to ciprofloxacin. The resistance rate of Enterobacteriaceae ranged from 0.0% for ciprofloxacin and chloramphenicol to 100.0% against amoxicillin/clavulanate. The prevalence of BV was higher than AV in pregnant women. This higher prevalence of BV suggests that measures should be taken to reduce the undesired consequences related to BV in the pregnancy. The circulation of drug-resistant bacteria in vaginal infections requires a global surveillance to reduce the risks to pregnant mothers and infants., Competing Interests: The authors have declared that no competing interests exist.

Aim: This study aims to develop and establish a computational model that can identify potent molecules for p21-activating kinase 1 (PAK1) Background: PAK1 is a well-established drug target that has been explored for various therapeutic interventions. Control of this protein requires an indispensable inhibitor to curb the structural changes and subsequent activation of signalling effectors responsible for the progression of diseases, such as cancer, inflammatory, viral, and neurological disorders., Objective: The study aims to establish a computational model that could identify active molecules which will further provide a platform for developing potential PAK1 inhibitors., Methods: A congeneric series of 27 compounds were considered for this study, with Ki (nm) covering a minimum of 3 log range. The compounds were developed based on a previously reported Group-I PAK inhibitor, namely G-5555. The 27 compounds were subjected to the SP and XP mode of docking to understand the binding mode, its conformation and interaction patterns. To understand the relevance of biological activity from computational approaches, the compounds were scored against generated water maps to obtain WM/MM ΔG binding energy. Moreover, molecular dynamics analysis was performed for the highly active compound to understand the conformational variability and stability of the complex. We then evaluated the predictable binding pose obtained from the docking studies., Results: From the SP and XP modes of docking, the common interaction pattern with the amino acid residues Arg299 (cation-π), Glu345 (Aromatic hydrogen bond), hinge region Leu347, salt bridges Asp393 and Asp407 was observed, among the congeneric compounds. The interaction pattern was compared with the co-crystal inhibitor FRAX597 of the PAK1 crystal structure (PDB id: 4EQC). The correlation with different docking parameters in the SP and XP modes was insignificant and thereby revealed that the SP and XP's scoring functions could not predict the active compounds. This was due to the limitations in the docking methodology that neglected the receptor flexibility and desolvation parameters. Hence, to recognise the desolvation and explicit solvent effects, as well as to study the Structure-Activity Relationships (SARs) extensively, WaterMap (WM) calculations were performed on the congeneric compounds. Based on displaceable unfavourable hydration sites (HS) and their associated thermodynamic properties, the WM calculations facilitated in understanding the significance of correlation in the folds of activity of highly active (19 and 17), moderately active (16 and 21) and less active (26 and 25) compounds. Furthermore, the scoring function from WaterMap, namely WM/MM, led to a significant R2 value of 0.72 due to a coupled conjunction with MM treatment and displaced unfavourable waters at the binding site. To check the "optimal binding conformation", molecular dynamics simulation was carried out with the highly active compound 19 to explain the binding mode, stability, interactions, solvent-accessible area, etc., which could support the predicted conformation with bioactive conformation., Conclusion: This study determined the best scoring function, established SARs and predicted active molecules through a computational model. This will contribute to the development of the most potent PAK1 inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)