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Lipoprotein(a) and diet: consuming sugar-sweetened beverages lowers lipoprotein(a) levels in obese and overweight adults.
Law, HG, Stanhope, KL, Zhang, W, Myagmarsuren, M, Jamshed, ZM, Khan, MA, Bang, H, Havel, PJ, Berglund, L, Enkhmaa, B
Journal of lipid research. 2024;(8):100588
Abstract
Lipoprotein(a) [Lp(a)] contributes to cardiovascular disease risk. A genetically determined size polymorphism in apolipoprotein(a) [apo(a)], determined by the number of Kringle (K) repeats, inversely regulates Lp(a) levels. Nongenetic factors including dietary saturated fat influence Lp(a) levels. However, less is known about the effects of carbohydrates including dietary sugars. In this double-blind, parallel arm study among 32 overweight/obese adults, we investigated the effect of consuming glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks on Lp(a) level and assessed the role of the apo(a) size polymorphism. The mean (±SD) age of participants was 54 ± 8 years, 50% were women, and 75% were of European descent. Following the 10-week intervention, Lp(a) level was reduced by an average (±SEM) of -13.2% ± 4.3% in all participants (P = 0.005); -15.3% ± 7.8% in the 15 participants who consumed glucose (P = 0.07); and -11.3% ± 4.5% in the 17 participants who consumed fructose (P = 0.02), without any significant difference in the effect between the two sugar groups. Relative changes in Lp(a) levels were similar across subgroups of lower versus higher baseline Lp(a) level or carrier versus noncarrier of an atherogenic small (≤22K) apo(a) size. In contrast, LDL-C increased. In conclusion, in older, overweight/obese adults, consuming sugar-sweetened beverages reduced Lp(a) levels by ∼13% independently of apo(a) size variability and the type of sugar consumed. The Lp(a) response was opposite to that of LDL-C and triglyceride concentrations. These findings suggest that metabolic pathways might impact Lp(a) levels.
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Anti-diarrheal effect of piperine possibly through the interaction with inflammation inducing enzymes: In vivo and in silico studies.
Afroz, M, Bhuia, MS, Rahman, MA, Hasan, R, Islam, T, Islam, MR, Chowdhury, R, Khan, MA, Antas E Silva, D, Melo Coutinho, HD, et al
European journal of pharmacology. 2024;:176289
Abstract
Piperine is a natural alkaloid that possesses a variety of therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and anticarcinogenic activities. The present study aims to assess the medicinal benefits of piperine as an anti-diarrheal agent in a chick model by utilizing in vivo and in silico techniques. For this, castor oil was administered orally to 2-day-old chicks to cause diarrhea. Bismuth subsalicylate (10 mg/kg), loperamide (3 mg/kg), and nifedipine (2.5 mg/kg) were used as positive controls, while the vehicle was utilized as a negative control. Two different doses (25 and 50 mg/kg b.w.) of the test sample (piperine) were administered orally, and the highest dose was tested with standards to investigate the synergistic activity of the test sample. In our findings, piperine prolonged the latent period while reducing the number of diarrheal feces in the experimental chicks during the monitoring period (4 h). At higher doses, piperine appears to reduce diarrheal secretion while increasing latency in chicks. Throughout the combined pharmacotherapy, piperine outperformed bismuth subsalicylate and nifedipine in terms of anti-diarrheal effects with loperamide. In molecular docking, piperine exhibited higher binding affinities towards different inflammatory enzymes such as cyclooxygenase 1 (-7.9 kcal/mol), cyclooxygenase 2 (-8.4 kcal/mol), nitric oxide synthases (-8.9 kcal/mol), and L-type calcium channel (-8.8 kcal/mol), indicating better interaction of PP with these proteins. In conclusion, piperine showed a potent anti-diarrheal effect in castor oil-induced diarrheal chicks by suppressing the inflammation and calcium ion influx induced by castor oil.
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Exploring the Efficacy of Sotagliflozin on Heart and Kidney Health in Diabetic Patients: A Comprehensive Meta-Analysis.
Nayudu, GSS, Benny, BM, Thomas, G, Khan, MA, Basutkar, RS
Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine. 2024;(2):269-278
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Abstract
Evidence for reducing cardiovascular and renal events with sotagliflozin is uncertain among type 2 diabetes mellitus (T2DM) patients. To gather more evidence, this meta-analysis assesses the beneficial effects of sotagliflozin, a dual sodium-glucose cotransporter 1 and 2 inhibitor, in reducing the cardiovascular and renal events in diabetic patients with or without chronic kidney disease (CKD). Scopus, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were the databases used to search. The studies published from January 1, 2018, to January 30, 2022, were considered. The eligibility of studies was assessed independently. The data were collected in a modified Cochrane data extraction form. The included studies' quality was assessed with the Cochrane risk-of-bias tool. The quality of evidence for renal and cardiovascular outcomes was evaluated using GRADEpro software. The number of events of urgent visits to the hospital and requiring hospitalization was reduced (RR: 0.73; 95% CI: 0.69, 0.78; P value <0.00001). The mortality rate because of cardiovascular events was decreased with sotagliflozin (RR: 0.73; 95% CI: 0.67, 0.80; P value <0.00001). Patients taking sotagliflozin had a drastic decline in the number of deaths due to stroke and non-fatal myocardial infarction. Yet, there is no difference between the groups in terms of changes in mortality due to other causes or the glomerular filtration rate (GFR). Sotagliflozin demonstrated effectiveness in reducing the mortality rate related to heart failure and cardiovascular events when the dose was increased from 200 mg to 400 mg. Despite this, evidence is still needed to prove the renal protective action.
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Comparison of TC-325 Hemostatic Powder with Standard Endoscopic Treatments for Malignancy-Related Upper Gastrointestinal Bleeding: Meta-Analysis of Randomized Controlled Trials.
Saeed, A, Yousuf, S, Hayat, MH, Haider, M, Aziz, M, Hayat, U, Salcedo, C, Tarar, ZI, Farooq, U, Sharma, S, et al
Digestive diseases and sciences. 2024
Abstract
BACKGROUND TC-325 powder has been successfully used in the management of malignancy-related upper gastrointestinal bleeding (UGIB) with favorable results. We conducted a meta-analysis of randomized controlled trials (RCTs) comparing TC-325 hemostatic powder with standard endoscopic treatments in the management of malignancy-related UGIB. METHODS Several databases were reviewed from inception to May 02, 2024 to identify RCTs comparing TC-325 and standard endoscopic treatments for the management of malignancy-related UGIB. Our outcomes of interest were immediate hemostasis, 30-day rebleeding, length of hospital stay, need for surgery, need for angiographic embolization, and all-cause mortality. We calculated pooled risk ratio (RR) with 95% confidence intervals (CI) for categorical variables and mean difference (MD) with 95% CI for continuous variables. We used a random effect model to analyze the data and heterogeneity was assessed by I2 statistic. RESULTS Four RCTs with 227 patients were included. We found that, the rate of immediate hemostasis was significantly higher in the TC-325 group compared to the standard therapy group, RR (95% CI): 1.48 (1.26, 1.74). There was no significant difference in 30-day rebleeding between the groups RR (95% CI): 0.52 (0.15, 1.76). We found no significant difference in other outcomes between groups such as the need for angiographic embolization, all-cause mortality, length of hospital stay, and need for surgery. CONCLUSIONS We found that, TC-325 hemostatic powder was superior to standard endoscopic treatments in achieving immediate hemostasis in patients with malignancy-related UGIB.
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Comparative efficacy of tocotrienol and tocopherol (vitamin E) on atherosclerotic cardiovascular diseases in humans.
Rafique, S, Khan, DA, Farhat, K, Khan, MA, Noor, M, Sharif, M
JPMA. The Journal of the Pakistan Medical Association. 2024;(6):1124-1129
Abstract
OBJECTIVE To compare the efficacy of tocotrienol and tocopherol in the management of patients with atherosclerotic cardiovascular diseases. METHODS The systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines 2020, and comprised literature search from 2002 till January 5, 2023, on PubMed, Google Scholar, Cochrane Library, Google, Wiley-Inter Science Library, Medline, SpringerLink, Taylor and Francis databases. The search was conducted using key words, such as: "tocopherol", "tocotrienol", "vitamin E", "dyslipidaemia", "cardiovascular diseases" "cardioprotective", "hypercholesterolemia" and "atherosclerosis" along with Boolean operators. Human clinical studies regarding the use of tocotrienol or tocopherol or comparison of its efficacy in patients having atherosclerosis, dyslipidaemia leading to cardiovascular diseases, and studies including details of efficacy of any of the four alpha, beta, gamma, delta isomers of tocopherol or tocotrienol were included. Pertinent data from the eligible studies was retrieved and reviewed. RESULTS Of the 516 articles identified, 26 (5%) articles met eligibility criteria. Of them 5(19%) were subjected to detailed analysis. Tocotrienol showed significant anti-oxidant efficacy at (250 mg/d) by decreasing cholesterol and serum inflammatory biomarkers i.e C-reactive protein (40%), malondialdehyde (34%), gamma-glutamyl transferase (22%) (p<0.001). Total anti-oxidant status (TAS) levels raised 22% (p<0.001) and Inflammatory cytokines i.e resistin, interleukin (IL)-1, IL-12, Interferon-gamma were decreased 15-17% (p<0.05-0.01) respectively by tocotrienol. Several microRNA (miRNA-133a, miRNA-223, miRNA-214, miRNA-155) were modulated by δ-tocotrienol. Whereas, tocopherol showed heterogeneity of results by either decreasing or increasing the risk of mortality in atherosclerotic cardiovascular diseases. CONCLUSION Compared to tocopherol, tocotrienol was found to be safe and potential candidate for improving cardiovascular health in the management of atherosclerotic cardiovascular diseases.
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An updated landscape on nanopharmaceutical delivery for mitigation of colon cancer.
Shahzad, M, Hameed, H, Amjad, A, Khan, MA, Qureshi, IS, Hameed, A, Saeed, A, Munir, R
Naunyn-Schmiedeberg's archives of pharmacology. 2024
Abstract
Globally, colorectal cancer (CRC) continues to rank among the leading causes of cancer-related death. Systemic toxicity, multidrug resistance, and nonspecific targeting often pose challenges to conventional therapy for CRC. Because it is a complex disease with a complex genetic and environmental pathophysiology, advanced therapeutic strategies are needed. Nanotechnology presents a potential solution that may maximize therapeutic efficacy while minimizing negative effects by enabling personalized delivery of anticancer drugs. This review focuses on recent developments in colorectal drug delivery systems based on nanotechnology. Numerous nanomaterials, including liposomes, dendrimers, micelles, exosomes, and gold nanoparticles, are developed and used. Distinctive characteristics of mentioned nanocarriers are discussed along with strategies that can be employed for enhancing the delivery of drugs to colorectal cancer cells. The review also quotes the most relevant preclinical and clinical studies that show how these nanomaterials improve drug solubility, stability, and targeted delivery while overcoming the shortcomings of conventional therapies. Nanotechnology has made CRC treatment very efficient and advanced, which has opened up new possibilities for targeted drug delivery. Preclinical and clinical studies have also proved that the use of nano-formulations in colon-specific delivery systems have significant results, indicating potential for better patient outcomes. Future research can be done in order to overcome the hurdles regarding biocompatibility, expansion, and regulatory challenges. Large-scale clinical trials and nanomaterial formulation optimization should be the main goals of future research to confirm the efficacy and safety of these novel treatments.
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SPECT/CT and PET/CT for the Evaluation of Persistent or Recurrent Pain After Spine Surgery: A Systematic Review and Case Series.
Awosika, T, Davidar, AD, Hersh, AM, Menta, A, Weber-Levine, C, Alomari, S, Khan, MA, Theodore, N
World neurosurgery. 2024;:e344-e359
Abstract
OBJECTIVE The differential diagnosis for postoperative back pain is broad, and conventional imaging modalities are not always conclusive. Therefore, we performed a systematic review of the literature and present case studies describing the use of single-photon emission CT (SPECT)/CT or positron emission tomography (PET)/CT in the diagnosis of back pain following spine surgery. METHODS A systematic review was conducted according to PRISMA guidelines across 5 databases. Relevant keywords included PET/CT, bone SPECT/CT, and pseudarthrosis. The studies were assessed for diagnostic accuracy of the imaging technologies. RESULTS A total of 2,444 studies were screened, 91 were selected for full-text review, and 21 were ultimately included. Six retrospective studies investigated the use of SPECT/CT with a total sample size of 309 patients. Two of these studies used SPECT/CT to predict screw loosening in over 50% of patients. Eight studies examined the use of 18-fluoride sodium fluoride (18F-NaF) PET/CT. Among these studies, measures of diagnostic accuracy varied but overall demonstrated the ability of 18F-NaF PET/CT to detect screw loosening and pseudarthrosis. Seven studies examined 18F-fluorodeoxyglucose (FDG) PET/CT and supported its utility in the diagnosis of postoperative infections in the spine. CONCLUSIONS PET/CT and SPECT/CT are useful in the evaluation of postoperative pain of the spine, especially in patients for whom conventional imaging modalities yield inconclusive results. More diagnostic accuracy studies with strong reference standards are needed to compare hybrid imaging to conventional imaging.
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Unveiling the therapeutic promise of natural products in alleviating drug-induced liver injury: Present advancements and future prospects.
Singh, D, Khan, MA, Siddique, HR
Phytotherapy research : PTR. 2024;(1):22-41
Abstract
Drug-induced liver injury (DILI) refers to adverse reactions to small chemical compounds, biological agents, and medical products. These reactions can manifest as acute or chronic damage to the liver. From 1997 to 2016, eight drugs, including troglitazone, nefazodone, and lumiracoxib, were removed from the market due to their liver-damaging effects, which can cause diseases. We aimed to review the recent research on natural products and their bioactive components as hepatoprotective agents in mitigating DILI. Recent articles were fetched via searching the PubMed, PMC, Google Scholar, and Web of Science electronic databases from 2010 to January 2023 using relevant keywords such as "natural products," "acetaminophen," "antibiotics," "paracetamol," "DILI," "hepatoprotective," "drug-induced liver injury," "liver failure," and "mitigation." The studies reveal that the antituberculosis drug (acetaminophen) is the most frequent cause of DILI, and natural products have been largely explored in alleviating acetaminophen-induced liver injury. They exert significant hepatoprotective effects by preventing mitochondrial dysfunction and inflammation, inhibiting oxidative/nitrative stress, and macromolecular damage. Due to the bioavailability and dietary nature, using natural products alone or as an adjuvant with existing drugs is promising. To advance DILI management, it is crucial to conduct well-designed randomized clinical trials to evaluate natural products' efficacy and develop new molecules clinically. However, natural products are a promising solution for remedying drug-induced hepatotoxicity and lowering the risk of DILI.
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Effect of Calorie Restriction and Intermittent Fasting Regimens on Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Humans: A Systematic Review.
Alkurd, R, Mahrous, L, Zeb, F, Khan, MA, Alhaj, H, Khraiwesh, HM, Faris, ME
Medicina (Kaunas, Lithuania). 2024;60(1)
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Plain language summary
Brain-derived neurotrophic factor (BDNF) is a protein that plays a crucial role in brain development, cognition and metabolism. Intermittent fasting (IF) is a promising therapeutic strategy for managing metabolic disorders and improving cognitive function. Therefore, this systematic review of sixteen experimental and observational studies investigated the effect of IF on BDNF production and improvements in cognition through the BDNF pathway in healthy adults and people with metabolic disorders. Included studies focused on different IF regimens such as calorie restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE) and Ramadan model of intermittent fasting (RIF) Future, well-controlled, long-term, robust studies are required to assess the effect of different IF regimens on the production of BDNF and cognitive function in people with metabolic disorders, as the current research is inconclusive. However, healthcare professionals can use the review to understand the potential beneficial effects of IF on cognition and metabolic health in humans.
Abstract
Background: The potential positive interaction between intermittent fasting (IF) and brain-derived neurotrophic factor (BDNF) on cognitive function has been widely discussed. This systematic review tried to assess the efficacy of interventions with different IF regimens on BDNF levels and their association with cognitive functions in humans. Interventions with different forms of IF such as caloric restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE), and the Ramadan model of intermittent fasting (RIF) were targeted. Methods: A systematic review was conducted for experimental and observational studies on healthy people and patients with diseases published in EMBASE, Scopus, PubMed, and Google Scholar databases from January 2000 to December 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statements (PRISMA) for writing this review. Results: Sixteen research works conducted on healthy people and patients with metabolic disorders met the inclusion criteria for this systematic review. Five studies showed a significant increase in BDNF after the intervention, while five studies reported a significant decrease in BDNF levels, and the other six studies showed no significant changes in BDNF levels due to IF regimens. Moreover, five studies examined the RIF protocol, of which, three studies showed a significant reduction, while two showed a significant increase in BDNF levels, along with an improvement in cognitive function after RIF. Conclusions: The current findings suggest that IF has varying effects on BDNF levels and cognitive functions in healthy, overweight/obese individuals and patients with metabolic conditions. However, few human studies have shown that IF increases BDNF levels, with controversial results. In humans, IF has yet to be fully investigated in terms of its long-term effect on BDNF and cognitive functions. Large-scale, well-controlled studies with high-quality data are warranted to elucidate the impact of the IF regimens on BDNF levels and cognitive functions.
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Synthesis, monomer conversion, and mechanical properties of polylysine based dental composites.
Lone, SB, Zeeshan, R, Khadim, H, Khan, MA, Khan, AS, Asif, A
Journal of the mechanical behavior of biomedical materials. 2024;:106398
Abstract
OBJECTIVE The aim of this study was to synthesize a new bioactive and antibacterial composite by incorporating reactive calcium phosphate and antibacterial polylysine into a resin matrix and evaluate the effect of these fillers on structural analysis, degree of monomer conversion, mechanical properties, and bioactivity of these newly developed polypropylene based dental composites. METHODOLOGY Stock monomers were prepared by mixing urethane dimethacrylate and polypropylene glycol dimethacrylate and combined with 40 wt% silica to make experimental control (E-C). The other three experimental groups contained a fixed percentage of silica (40 wt%), monocalcium phosphate monohydrate, and β-tri calcium phosphate (5 wt% each) with varying amounts of polylysine (PL). These groups include E-CCP0 (0 wt% PL), E-CCP5 (5 wt% PL) and E-CCP10 (10 wt% PL). The commercial control used was Filtek™ Z250 3M ESPE. The degree of conversion was assessed by using Fourier transform infrared spectroscopy (FTIR). Compressive strength and Vicker's micro hardness testing were evaluated after 24 h of curing the samples. For bioactivity, prepared samples were placed in simulated body fluid for 0, 1, 7, and 28 days and were analyzed using a scanning electron microscope (SEM). SPSS 23 was used to analyze the data and one-way ANOVA and post hoc tukey's test were done, where the significant level was set ≤0.05. RESULTS Group E-C showed better mechanical properties than other experimental and commercial control groups. Group E-C showed the highest degree of conversion (72.72 ± 1.69%) followed by E-CCP0 (72.43 ± 1.47%), Z250 (72.26 ± 1.75%), E-CCP10 (71.07 ± 0.19%), and lowest value was shown by E-CCP5 (68.85 ± 7.23%). In shear bond testing the maximum value was obtained by E-C. The order in decreasing value of bond strength is E-C (8.13 ± 3.5 MPa) > Z250 (2.15 ± 1.1 MPa) > E-CCP10 (2.08 ± 2.1 MPa) > E-CCP5 (0.94 ± 0.8 MPa) > E-CCP0 (0.66 ± 0.2 MPa). In compressive testing, the maximum strength was observed by commercial control i.e., Z250 (210.36 ± 18 MPa) and E-C (206.55 ± 23 MPa), followed by E-CCP0 (108.06 ± 19 MPa), E-CCP5 (94.16 ± 9 MPa), and E-CCP10 (80.80 ± 13 MPa). The maximum number of hardness was shown by E-C (93.04 ± 8.23) followed by E-CCP0 (38.93 ± 9.21) > E-CCP10 (35.21 ± 12.31) > E-CCP5 (34.34 ± 12.49) > Z250 (25 ± 2.61). SEM images showed that the maximum apatite layer as shown by E-CCP10 and the order followed as E-CCP10 > E-CCP5 > E-CCP0 >Z250> E-C. CONCLUSION The experimental formulation showed an optimal degree of conversion with compromised mechanical properties when the polylysine percentage was increased. Apatite layer formation and polylysine at the interface may result in remineralization and ultimately lead to the prevention of secondary caries formation.
