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  1. Wei L, Bee MY, Poh SC, Garg A, Lin F, Gao J
    Environ Monit Assess, 2022 Dec 27;195(1):231.
    PMID: 36572829 DOI: 10.1007/s10661-022-10822-1
    The marine aquaculture industry has caused a suite of adverse environmental consequences, including offshore eutrophication. However, little is known about the extent to which aquaculture effluents affect nearby wetland ecosystems. We carried out a field experiment in a mangrove stand located between two effluent-receiving creeks to estimate the extent to which marine aquaculture affects the soil nutrient distribution and plant nutrient status of adjacent mangroves. Carbon (C), nitrogen (N), and phosphorus (P) contents and C isotopic signatures were determined seasonally in creeks, pore water, surface soils, and in the leaves of the dominant mangrove species Kandelia obovata. The creeks exhibited nutrient enrichment (2.44 mg N L-1 and 0.09 mg P L-1 on average). The soils had N (from 1.40 to 2.70 g kg-1) and P (from 0.58 to 2.76 g kg-1) much greater than those of pristine mangrove forests. Combined analyses of the N:P ratio, nutrient resorption efficiency, and proficiency indicated that soil P met plant demands, but plants in most plots showed N limitation, suggesting that soil nutrient accumulation did not fundamentally impact the plant nutrient status. Collectively, this case study shows that marine aquaculture farms can affect adjacent mangrove stands even though their effluents are not directly discharged into the mangrove stands, but mangrove forests may have substantial buffering capabilities for long-term nutrient loading.
  2. Ashique S, Mishra N, Mohanto S, Garg A, Taghizadeh-Hesary F, Gowda BHJ, et al.
    Heliyon, 2024 Feb 29;10(4):e25754.
    PMID: 38370192 DOI: 10.1016/j.heliyon.2024.e25754
    The impact of the coronavirus disease 2019 (COVID-19) pandemic on the everyday livelihood of people has been monumental and unparalleled. Although the pandemic has vastly affected the global healthcare system, it has also been a platform to promote and develop pioneering applications based on autonomic artificial intelligence (AI) technology with therapeutic significance in combating the pandemic. Artificial intelligence has successfully demonstrated that it can reduce the probability of human-to-human infectivity of the virus through evaluation, analysis, and triangulation of existing data on the infectivity and spread of the virus. This review talks about the applications and significance of modern robotic and automated systems that may assist in spreading a pandemic. In addition, this study discusses intelligent wearable devices and how they could be helpful throughout the COVID-19 pandemic.
  3. Tayyeb JZ, Priya M, Guru A, Kishore Kumar MS, Giri J, Garg A, et al.
    Mol Biol Rep, 2024 Mar 15;51(1):423.
    PMID: 38489102 DOI: 10.1007/s11033-024-09407-7
    BACKGROUND: Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties.

    METHODS: In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity.

    RESULTS: ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40 µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10 µg/mL, 20 µg/mL, 40 µg/mL, and 80 µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells.

    CONCLUSIONS: This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.

  4. Ashique S, Garg A, Mishra N, Raina N, Ming LC, Tulli HS, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Nov;396(11):2769-2792.
    PMID: 37219615 DOI: 10.1007/s00210-023-02522-5
    Lung cancer is the most common type of cancer, with over 2.1 million cases diagnosed annually worldwide. It has a high incidence and mortality rate, leading to extensive research into various treatment options, including the use of nanomaterial-based carriers for drug delivery. With regard to cancer treatment, the distinct biological and physico-chemical features of nano-structures have acquired considerable impetus as drug delivery system (DDS) for delivering medication combinations or combining diagnostics and targeted therapy. This review focuses on the use of nanomedicine-based drug delivery systems in the treatment of lung cancer, including the use of lipid, polymer, and carbon-based nanomaterials for traditional therapies such as chemotherapy, radiotherapy, and phototherapy. The review also discusses the potential of stimuli-responsive nanomaterials for drug delivery in lung cancer, and the limitations and opportunities for improving the design of nano-based materials for the treatment of non-small cell lung cancer (NSCLC).
  5. Ashique S, Mishra N, Garg A, Kumar N, Khan Z, Mohanto S, et al.
    Arch Bronconeumol, 2024 May 06.
    PMID: 38755052 DOI: 10.1016/j.arbres.2024.04.030
    Lung cancer remains the leading cause of cancer-related deaths worldwide. According to the American Cancer Society (ACS), it ranks as the second most prevalent type of cancer globally. Recent findings have highlighted bidirectional gut-lung interactions, known as the gut-lung axis, in the pathophysiology of lung cancer. Probiotics are live microorganisms that boost host immunity when consumed adequately. The immunoregulatory mechanisms of probiotics are thought to operate through the generation of various metabolites that impact both the gut and distant organs (e.g., the lungs) through blood. Several randomized controlled trials have highlighted the pivotal role of probiotics in gut health especially for the prevention and treatment of malignancies, with a specific emphasis on lung cancer. Current research indicates that probiotic supplementation positively affects patients, leading to a suppression in cancer symptoms and a shortened disease course. While clinical trials validate the therapeutic benefits of probiotics, their precise mechanism of action remains unclear. This narrative review aims to provide a comprehensive overview of the present landscape of probiotics in the management of lung cancer.
  6. Ashique S, Mohanto S, Ahmed MG, Mishra N, Garg A, Chellappan DK, et al.
    Heliyon, 2024 Jul 15;10(13):e34092.
    PMID: 39071627 DOI: 10.1016/j.heliyon.2024.e34092
    The microbiota-gut-brain axis (MGBA) represents a sophisticated communication network between the brain and the gut, involving immunological, endocrinological, and neural mediators. This bidirectional interaction is facilitated through the vagus nerve, sympathetic and parasympathetic fibers, and is regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Evidence shows that alterations in gut microbiota composition, or dysbiosis, significantly impact neurological disorders (NDs) like anxiety, depression, autism, Parkinson's disease (PD), and Alzheimer's disease (AD). Dysbiosis can affect the central nervous system (CNS) via neuroinflammation and microglial activation, highlighting the importance of the microbiota-gut-brain axis (MGBA) in disease pathogenesis. The microbiota influences the immune system by modulating chemokines and cytokines, impacting neuronal health. Synbiotics have shown promise in treating NDs by enhancing cognitive function and reducing inflammation. The gut microbiota's role in producing neurotransmitters and neuroactive compounds, such as short-chain fatty acids (SCFAs), is critical for CNS homeostasis. Therapeutic interventions targeting the MGBA, including dietary modulation and synbiotic supplementation, offer potential benefits for managing neurodegenerative disorders. However, more in-depth clinical studies are necessary to fully understand and harness the therapeutic potential of the MGBA in neurological health and disease.
  7. Ashique S, Mishra N, Mantry S, Garg A, Kumar N, Gupta M, et al.
    PMID: 39196392 DOI: 10.1007/s00210-024-03392-1
    A significant number of deaths and disabilities worldwide are brought on by inflammatory lung diseases. Many inflammatory lung disorders, including chronic respiratory emphysema, resistant asthma, resistance to steroids, and coronavirus-infected lung infections, have severe variants for which there are no viable treatments; as a result, new treatment alternatives are needed. Here, we emphasize how oxidative imbalance contributes to the emergence of provocative lung problems that are challenging to treat. Endogenic antioxidant systems are not enough to avert free radical-mediated damage due to the induced overproduction of ROS. Pro-inflammatory mediators are then produced due to intracellular signaling events, which can harm the tissue and worsen the inflammatory response. Overproduction of ROS causes oxidative stress, which causes lung damage and various disease conditions. Invasive microorganisms or hazardous substances that are inhaled repeatedly can cause an excessive amount of ROS to be produced. By starting signal transduction pathways, increased ROS generation during inflammation may cause recurrent DNA damage and apoptosis and activate proto-oncogenes. This review provides information about new targets for conducting research in related domains or target factors to prevent, control, or treat such inflammatory oxidative stress-induced inflammatory lung disorders.
  8. Ashique S, Mishra N, Garg A, Sibuh BZ, Taneja P, Rai G, et al.
    Front Nutr, 2023;10:1126579.
    PMID: 37545572 DOI: 10.3389/fnut.2023.1126579
    Ulcerative colitis (UC) is presently considered a multifactorial pathology, which may lead to persistent inflammatory action of the gastrointestinal tract (GIT) because of an improperly managed immunological reactivity to the intestinal microbiota found in the GIT. The immune response to common commensal microbes plays an essential role in intestinal inflammation related to UC synbiotics, and it is an important element in the optimal therapy of UC. Therefore, synbiotics, i.e., a mixture of prebiotics and probiotics, may help control the diseased state. Synbiotics alleviate the inflammation of the colon by lowering the reactive oxygen species (ROS) and improving the level of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Prebiotic supplementation is not a common practice at the moment, despite numerous research findings proving that the benefits of both probiotics and prebiotics encourage their continued existence and positioning in the GIT, with positive effects on human health by managing the inflammatory response. However, the fact that there have been fewer studies on the treatment of UC with different probiotics coupled with selected prebiotics, i.e., synbiotics, and the outcomes of these studies have been very favorable. This evidence-based study explores the possible role of ROS, SOD, and synbiotics in managing the UC. The proposed review also focuses on the role of alteration of gut microbiota, antioxidant defense in the gastrointestinal tract, and the management of UC. Thus, the current article emphasizes oxidative stress signaling in the GI tract, oxidative stress-based pathomechanisms in UC patients, and UC therapies inhibiting oxidative stress' effects.
  9. Garg A, Keng WT, Chen Z, Sathe AA, Xing C, Kailasam PD, et al.
    J Clin Invest, 2022 Dec 01;132(23).
    PMID: 36282599 DOI: 10.1172/JCI156864
    Multiple genetic loci have been reported for progeroid syndromes. However, the molecular defects in some extremely rare forms of progeria have yet to be elucidated. Here, we report a 21-year-old man of Chinese ancestry who has an autosomal recessive form of progeria, characterized by severe dwarfism, mandibular hypoplasia, hyperopia, and partial lipodystrophy. Analyses of exome sequencing data from the entire family revealed only 1 rare homozygous missense variant (c.86C>T; p.Pro29Leu) in TOMM7 in the proband, while the parents and 2 unaffected siblings were heterozygous for the variant. TOMM7, a nuclear gene, encodes a translocase in the outer mitochondrial membrane. The TOMM complex makes up the outer membrane pore, which is responsible for importing many preproteins into the mitochondria. A proteomic comparison of mitochondria from control and proband-derived cultured fibroblasts revealed an increase in abundance of several proteins involved in oxidative phosphorylation, as well as a reduction in abundance of proteins involved in phospholipid metabolism. We also observed elevated basal and maximal oxygen consumption rates in the fibroblasts from the proband as compared with control fibroblasts. We concluded that altered mitochondrial protein import due to biallelic loss-of-function TOMM7 can cause severe growth retardation and progeroid features.
  10. Ashique S, De Rubis G, Sirohi E, Mishra N, Rihan M, Garg A, et al.
    Chem Biol Interact, 2022 Dec 01;368:110231.
    PMID: 36288778 DOI: 10.1016/j.cbi.2022.110231
    The human microbiota is fundamental to correct immune system development and balance. Dysbiosis, or microbial content alteration in the gut and respiratory tract, is associated with immune system dysfunction and lung disease development. The microbiota's influence on human health and disease is exerted through the abundance of metabolites produced by resident microorganisms, where short-chain fatty acids (SCFAs) represent the fundamental class. SCFAs are mainly produced by the gut microbiota through anaerobic fermentation of dietary fibers, and are known to influence the homeostasis, susceptibility to and outcome of many lung diseases. This article explores the microbial species found in healthy human gastrointestinal and respiratory tracts. We investigate factors contributing to dysbiosis in lung illness, and the gut-lung axis and its association with lung diseases, with a particular focus on the functions and mechanistic roles of SCFAs in these processes. The key focus of this review is a discussion of the main metabolites of the intestinal microbiota that contribute to host-pathogen interactions: SCFAs, which are formed by anaerobic fermentation. These metabolites include propionate, acetate, and butyrate, and are crucial for the preservation of immune homeostasis. Evidence suggests that SCFAs prevent infections by directly affecting host immune signaling. This review covers the various and intricate ways through which SCFAs affect the immune system's response to infections, with a focus on pulmonary diseases including chronic obstructive pulmonary diseases, asthma, lung cystic fibrosis, and tuberculosis. The findings reviewed suggest that the immunological state of the lung may be indirectly influenced by elements produced by the gut microbiota. SCFAs represent valuable potential therapeutic candidates in this context.
  11. Schutz FAB, Sirachainan E, Kuppusamy S, Hoa NTT, Dejthevaporn T, Bahadzor B, et al.
    Ther Adv Med Oncol, 2021;13:1758835920985464.
    PMID: 33747148 DOI: 10.1177/1758835920985464
    AIMS: Clinical decision making is challenging in men with metastatic prostate cancer (mPC), as heterogeneity in treatment options and patient characteristics have resulted in multiple scenarios with little or no evidence. The South East Asia Expert Panel 2019 addressed some of these challenges.

    METHODS: Based on evidence in the literature and expert interviews, 19 statements were formulated for key challenges in the treatment of men with castration-sensitive and -resistant prostate cancer in clinical practice. A modified Delphi process was used to reach consensus among experts in the panel and develop clinical practice recommendations.

    RESULTS: The majority of the panel preferred a risk-based stratification and recommended abiraterone or enzalutamide as first-line therapy for symptomatic chemotherapy naïve patients. Abiraterone is preferred over enzalutamide as a first-line treatment in these patients. However, the panel did not support the use of abiraterone in high risk lymph-node positive only (N+M0) or in non-metastatic (N0M0) patients. In select patients, low dose abiraterone with food may be used to optimize clinical outcomes. Androgen receptor gene splice variant status may be a useful guide to therapy. In addition, generic versions of approved therapies may improve access to treatment to a broader patient population. The choice of treatment, as well as sequencing are guided by both patient and disease characteristics, preferences, drug access, cost, and compliance.

    CONCLUSION: Expert recommendations are key to guidance for the optimal management of mPC. Appropriate choice, timing, and sequence of treatment options can help to tailor therapy to maximize outcomes in men with mPC.

  12. Thorlacius L, Garg A, Ingram JR, Villumsen B, Theut Riis P, Gottlieb AB, et al.
    Br J Dermatol, 2018 03;178(3):715-721.
    PMID: 29080368 DOI: 10.1111/bjd.16093
    BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items.

    OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains.

    METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey.

    RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments.

    CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

  13. Mastacouris N, Tannenbaum R, Strunk A, Koptyev J, Aarts P, Alhusayen R, et al.
    JAMA Dermatol, 2023 Nov 01;159(11):1258-1266.
    PMID: 37755725 DOI: 10.1001/jamadermatol.2023.3282
    IMPORTANCE: Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines.

    OBJECTIVE: To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied.

    EVIDENCE REVIEW: Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice.

    FINDINGS: Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]).

    CONCLUSIONS AND RELEVANCE: An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting.

  14. Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al.
    Anesthesiology, 2014 Mar;120(3):564-78.
    PMID: 24534856 DOI: 10.1097/ALN.0000000000000113
    BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS.

    METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria.

    RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom.

    CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

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