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1.
Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways.
Sinha, JK, Trisal, A, Ghosh, S, Gupta, S, Singh, KK, Han, SS, Mahapatra, M, Abomughaid, MM, Abomughayedh, AM, Almutary, AG, et al
Ageing research reviews. 2024;:102211
Abstract
Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly dementia, have not been fully explored. In recent years, studies have revealed the modulatory and beneficial effects of psychedelics in the context of dementia, specifically Alzheimer's disease (AD)-related dementia, which lacks a definitive cure. Psychedelics such as N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and Psilocybin have shown potential in mitigating the effects of this debilitating disease. These compounds not only target neurotransmitter imbalances but also act at the molecular level to modulate signalling pathways in AD, including the brain-derived neurotrophic factor signalling pathway and the subsequent activation of mammalian target of rapamycin and other autophagy regulators. Therefore, the controlled and dose-dependent administration of psychedelics represents a novel therapeutic intervention worth exploring and considering for the development of drugs for the treatment of AD-related dementia. In this article, we critically examined the literature that sheds light on the therapeutic possibilities and pathways of psychedelics for AD-related dementia. While this emerging field of research holds great promise, further studies are necessary to elucidate the long-term safety, efficacy, and optimal treatment protocols. Ultimately, the integration of psychedelics into the current treatment paradigm may provide a transformative approach for addressing the unmet needs of individuals living with AD-related dementia and their caregivers.
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2.
Unveiling the impact of Aging on BBB and Alzheimer's disease: Factors and Therapeutic implications.
Jha, NK, Kumar Nelson, V, Nuli, MV, Kanna, S, Gahtani, RM, Hani, U, Singh, AK, Gupta, S, Abomughaid, MM, Abomughayedh, AM, et al
Ageing research reviews. 2024;:102224
Abstract
Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that has devastating effects on individuals, often resulting in dementia. AD is primarily defined by the presence of extracellular plaques containing insoluble β-amyloid peptide (Aβ) and neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein (P-tau). In addition, individuals afflicted by these age-related illnesses experience a diminished state of health, which places significant financial strain on their loved ones. Several risk factors play a significant role in the development of AD. These factors include genetics, diet, smoking, certain diseases (such as cerebrovascular diseases, obesity, hypertension, and dyslipidemia), age, and alcohol consumption. Age-related factors are key contributors to the development of vascular-based neurodegenerative diseases such as AD. In general, the process of aging can lead to changes in the immune system's responses and can also initiate inflammation in the brain. The chronic inflammation and the inflammatory mediators found in the brain play a crucial role in the dysfunction of the blood-brain barrier (BBB). Furthermore, maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. Therefore, in this review, we discussed the role of age and its related factors in the breakdown of the blood-brain barrier and the development of AD. We also discussed the importance of different compounds, such as those with anti-aging properties, and other compounds that can help maintain the integrity of the blood-brain barrier in the prevention of AD. This review builds a strong correlation between age-related factors, degradation of the BBB, and its impact on AD.
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Artificial Intelligence in Coronary Artery Calcium Scoring Detection and Quantification.
Abdelrahman, K, Shiyovich, A, Huck, DM, Berman, AN, Weber, B, Gupta, S, Cardoso, R, Blankstein, R
Diagnostics (Basel, Switzerland). 2024;(2)
Abstract
Coronary artery calcium (CAC) is a marker of coronary atherosclerosis, and the presence and severity of CAC have been shown to be powerful predictors of future cardiovascular events. Due to its value in risk discrimination and reclassification beyond traditional risk factors, CAC has been supported by recent guidelines, particularly for the purposes of informing shared decision-making regarding the use of preventive therapies. In addition to dedicated ECG-gated CAC scans, the presence and severity of CAC can also be accurately estimated on non-contrast chest computed tomography scans performed for other clinical indications. However, the presence of such "incidental" CAC is rarely reported. Advances in artificial intelligence have now enabled automatic CAC scoring for both cardiac and non-cardiac CT scans. Various AI approaches, from rule-based models to machine learning algorithms and deep learning, have been applied to automate CAC scoring. Convolutional neural networks, a deep learning technique, have had the most successful approach, with high agreement with manual scoring demonstrated in multiple studies. Such automated CAC measurements may enable wider and more accurate detection of CAC from non-gated CT studies, thus improving the efficiency of healthcare systems to identify and treat previously undiagnosed coronary artery disease.
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Glycolytic enzymes in non-glycolytic web: functional analysis of the key players.
Malla, A, Gupta, S, Sur, R
Cell biochemistry and biophysics. 2024
Abstract
To survive in the tumour microenvironment, cancer cells undergo rapid metabolic reprograming and adaptability. One of the key characteristics of cancer is increased glycolytic selectivity and decreased oxidative phosphorylation (OXPHOS). Apart from ATP synthesis, glycolysis is also responsible for NADH regeneration and macromolecular biosynthesis, such as amino acid biosynthesis and nucleotide biosynthesis. This allows cancer cells to survive and proliferate even in low-nutrient and oxygen conditions, making glycolytic enzymes a promising target for various anti-cancer agents. Oncogenic activation is also caused by the uncontrolled production and activity of glycolytic enzymes. Nevertheless, in addition to conventional glycolytic processes, some glycolytic enzymes are involved in non-canonical functions such as transcriptional regulation, autophagy, epigenetic changes, inflammation, various signaling cascades, redox regulation, oxidative stress, obesity and fatty acid metabolism, diabetes and neurodegenerative disorders, and hypoxia. The mechanisms underlying the non-canonical glycolytic enzyme activities are still not comprehensive. This review summarizes the current findings on the mechanisms fundamental to the non-glycolytic actions of glycolytic enzymes and their intermediates in maintaining the tumor microenvironment.
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Efficacy of immune checkpoint inhibitors combinations as first-line systemic treatment in patients with advanced urothelial carcinoma: A systematic review and network meta-analysis.
Monteiro, FSM, Soares, A, Mollica, V, Leite, CA, Carneiro, APCD, Rizzo, A, Bourlon, MT, Sasse, AD, Santoni, M, Gupta, S, et al
Critical reviews in oncology/hematology. 2024;:104321
Abstract
BACKGROUND Combinations of immune checkpoint inhibitors (ICI) with platinum-based chemotherapy (PlatinumCT) or with another ICI in the first-line setting for patients with metastatic urothelial carcinoma (mUC) have mixed results. METHODS Records were searched electronically from January 2019 to January 2024. A meta-analysis was performed to evaluate OS, progression-free survival (PFS), and overall response rate (ORR). RESULTS Immune-based combinations were associated with an OS (HR: 0.75; 95% CI: 0.61-0.92; p < 0.001; I2= 84.1%) and PFS benefit in the intention-to-treat population (HR: 0.67; 95%CI: 0.51-0.89; p < 0.001; I2 = 89.7%). There was no ORR improvement with immune-based combinations (HR: 1.36; 95% CI:0.84-2.20; p < 0.001; I2 = 92.6%). CONCLUSION This systematic review and study-level meta-analysis demonstrated that the immune-based combinations in first-line treatment for patients with mUC are associated with survival benefit.
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Are People With Type 1 Diabetes Mellitus Appropriately Following Insulin Injection Technique Practices: A Review of Literature.
Gupta, S, Ramteke, H, Gupta, S, Gupta, S, Gupta, KS
Cureus. 2024;(1):e51494
Abstract
People with type 1 diabetes mellitus (T1DM) need to take multiple doses of insulin injections daily throughout their lives. However, a notable portion of people with diabetes mellitus (DM) show suboptimal insulin injection technique practices. They are supposed to follow the recommended insulin injection technique guidelines. Our explorative literature search, including studies from the past 30 years, is expected to identify the deficiencies of self-injection insulin techniques and the associated complications in people with T1DM, where we have summarised the overall incidence of complications that have occurred due to nonadherence of the prescribed guidelines, along with their associated risk factors. We have attempted to include multiple systematic reviews, meta-analyses, literature reviews, case reports, and original articles from the search engines and databases like PubMed, Scopus, ScienceDirect, Cochrane Library, Google Scholar, and BioMed Central, and studies with only human participants were included in this search. The knowledge sharing from this research may be utilised for enhancing the structured education diabetes programme and implementing the population-based corrective measures, including the thrust areas in future multi-centre longitudinal research studies and recommendations, which can prevent unnecessary complications and enhance their quality of life. Correct insulin administration technique, abstaining from administration of injection at the areas with lipohypertrophy, rotation of injection sites, and ultrasound scanning can be used as a complimentary method to detect the lipohypertrophy at an early stage. Liposuction is beneficial in reducing the extensive lipohypertrophic tissues but helps achieve only cosmetically satisfactory outcome; thus, empowering people to follow insulin injection technique guidelines is one of the best strategies to reduce the high prevalence of lipohypertrophy. To conclude, education among the people with DM, especially T1DM who have to take insulin regularly, needs to be carried out consistently in the clinical settings, to prevent the severe complications caused due to inappropriate insulin injection techniques.
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7.
Review: Nutrient-nutrient interactions governing underground plant adaptation strategies in a heterogeneous environment.
Singh, K, Gupta, S, Singh, AP
Plant science : an international journal of experimental plant biology. 2024;:112024
Abstract
Plant growth relies on the mineral nutrients present in the rhizosphere. The distribution of nutrients in soils varies depending on their mobility and capacity to bind with soil particles. Consequently, plants often encounter either low or high levels of nutrients in the rhizosphere. Plant roots are the essential organs that sense changes in soil mineral content, leading to the activation of signaling pathways associated with the adjustment of plant architecture and metabolic responses. During differential availability of minerals in the rhizosphere, plants trigger adaptation strategies such as cellular remobilization of minerals, secretion of organic molecules, and the attenuation or enhancement of root growth to balance nutrient uptake. The interdependency, availability, and uptake of minerals, such as phosphorus (P), iron (Fe), zinc (Zn), potassium (K), nitrogen (N) forms, nitrate (NO3-), and ammonium (NH4+), modulate the root architecture and metabolic functioning of plants. Here, we summarized the interactions of major nutrients (N, P, K, Fe, Zn) in shaping root architecture, physiological responses, genetic components involved, and address the current challenges associated with nutrient-nutrient interactions. Furthermore, we discuss the major gaps and opportunities in the field for developing plants with improved nutrient uptake and use efficiency for sustainable agriculture.
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8.
Birth Cohort Colorectal Cancer (CRC): Implications for Research and Practice.
Gupta, S, May, FP, Kupfer, SS, Murphy, CC
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024;(3):455-469.e7
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Abstract
Colorectal cancer (CRC) epidemiology is changing due to a birth cohort effect, first recognized by increasing incidence of early onset CRC (EOCRC, age <50 years). In this paper, we define "birth cohort CRC" as the observed phenomenon, among individuals born 1960 and later, of increasing CRC risk across successive birth cohorts, rising EOCRC incidence, increasing incidence among individuals aged 50 to 54 years, and flattening of prior decreasing incidence among individuals aged 55 to 74 years. We demonstrate birth cohort CRC is associated with unique features, including increasing rectal cancer (greater than colon) and distant (greater than local) stage CRC diagnosis, and increasing EOCRC across all racial/ethnic groups. We review potential risk factors, etiologies, and mechanisms for birth cohort CRC, using EOCRC as a starting point and describing importance of viewing these through the lens of birth cohort. We also outline implications of birth cohort CRC for epidemiologic and translational research, as well as current clinical practice. We postulate that recognition of birth cohort CRC as an entity-including and extending beyond rising EOCRC-can advance understanding of risk factors, etiologies, and mechanisms, and address the public health consequences of changing CRC epidemiology.
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Association between calcium supplementation and gestational hypertension, and preeclampsia: A Meta-analysis of 26 randomized controlled trials.
Jaiswal, V, Joshi, A, Jha, M, Hanif, M, Arora, A, Gupta, S, Shah, M, Deb, N, Peng Ang, S, Aujla, S, et al
Current problems in cardiology. 2024;(3):102217
Abstract
BACKGROUND Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive disorders of pregnancy has been the ultimate priority in recent years. We aim to evaluate the association between calcium supplementation and preeclampsia and gestational hypertension risk among pregnant women. METHODS A systematic literature search was performed in electronic databases from inception to 15th July 2023, including only randomized controlled trials. Odds ratio (OR) were, and their corresponding 95% confidence interval (95% CI). RESULTS A total of 26 studies with 20,038 patients (10,003 patients with calcium supplements and 10,035 patients with placebo group) were included in the analysis. The Pooled analysis of primary outcome shows that calcium supplements reduce the risk of preeclampsia by 49% (OR, 0.51(95%CI: 0.40-0.66), P<0.001), and reduce the risk of gestational hypertension by 30% (OR, 0.70 (95%CI: 0.58-0.85)), P<0.001) compared to placebo. There was a trend of lower incidence of preterm delivery (OR, 0.88 (95%CI: 0.71-1.09), P=0.23), labor induction (OR, 0.90 (95%CI: 0.78-1.03), P=0.13), small for gestational age (OR, 0.70 (95% CI:0.37-1.32), P = 0.27), low birth weight (OR, 0.96 (95%CI: 0.86-1.08), P=0.53), perinatal mortality (OR, 0.88 (95%CI: 0.72-1.09), P=0.24), and maternal mortality (OR, 0.48 (95%CI: 0.12-1.84), P=0.28) among calcium supplementation group compared with the placebo group, however, statistical signifance was not achieved. CONCLUSION This study shows that calcium supplements are associated with a significant reduction in the risk of preeclampsia and gestational hypertension and a trend toward better maternal and fetal-related outcomes.
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A comprehensive review of small molecules targeting PI3K pathway: Exploring the structural development for the treatment of breast cancer.
Dubey, R, Sharma, A, Gupta, S, Gupta, GD, Asati, V
Bioorganic chemistry. 2024;:107077
Abstract
Cancer stands as one of the deadliest diseases, ranking second in terms of its global impact. Despite the presence of numerous compelling theories concerning its origins, none have succeeded in fully elucidating the intricate nature of this ailment. Among the prevailing concerns in today's world, breast cancer proliferation remains a significant issue, particularly affecting females. The abnormal proliferation of the PI3K pathway emerges as a prominent driver of breast cancer, underscoring its role in cellular survival and proliferation. Consequently, targeting this pathway has emerged as a leading strategy in breast cancer therapeutics. Within this context, the present article explores the current landscape of anti-tumour drug development, focusing on structural activity relationships (SAR) in PI3K targeting breast cancer treatment. Notably, certain moieties like triazines, pyrimidine, quinazoline, quinoline, and pyridoxine have been explored as potential PI3K inhibitors for combating breast cancer. Various heterocyclic small molecules are undergoing clinical trials, such as Alpelisib, the first orally available FDA-approved drug targeting PI3K; others include buparlisib, pictilisib, and taselisib, which inhibit class I PI3K. These drugs are used for the treatment of breast cancer but still have various side effects with their high cost. Therefore, the primary goal of this review is to include all current advances in the development of anticancer medicines that target PI3K over-activation in the treatment of breast cancer.