From dyes to drugs: The historical impact and future potential of dyes in drug discovery.

In the late 19th century, progress in dye chemistry led to advances in industrial organic chemistry in Germany. Over the next few decades, this revealed dyes not just as color agents but as promising lead compounds for drug development. Collaborations between dye chemists and medical researchers were crucial in turning these unexpected discoveries into structured medicinal chemistry efforts. The outcomes included major drug classes like sulfa antibiotics, antifungal azoles, and others, resulting in a legacy where dyes served not only as biological stains but as crucial tools for understanding complex natural products and drug interactions. Today, the impact of dye molecules persists in clinical therapies, molecular probing, pharmacokinetic tracing, and high-throughput screening. This review underscores the historical contributions shaping contemporary pharmaceutical sciences, highlighting the role of dyes as indispensable tools propelling drug discovery across generations.

The role of probiotics on microvascular complications of type-2 diabetes: Nephropathy and retinopathy.

Diabetes is a multifactorial disorder that involves several molecular mechanisms and is still one of the key global health challenges with increasing prevalence and incidence. Gut microbiome dysbiosis could activate and recognize receptors that trigger the inflammation response and modulation of insulin sensitivity. In addition, the intricate role of gut microbiota dysbiosis in the onset and development of T2D (Type 2 diabetes mellitus) and associated microvascular complications was identified. These complications include diabetic nephropathy (DN) and diabetic retinopathy (DR), diabetic neuropathy, cerebrovascular disorders, and coronary heart disease. A recent interesting strategy to improve these complications is probiotics administration. The safety and health effects of probiotics against various diseases have been validated by various in vitro, in vivo and clinical studies. In this review, the related mechanisms between the gut microbiome, initiation, and progression of T2D and its common microvascular complications (DN and DR) have been discussed.

Clinical Application of Artificial Intelligence in Prediction of Intraoperative Cerebrospinal Fluid Leakage in Pituitary Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative cerebrospinal fluid (CSF) leakage is the leading adverse event in transsphenoidal surgery (TSS). Intraoperative CSF (ioCSF) leakage is one of the most important predictive factors for postoperative CSF leakage. This systematic review and meta-analysis aimed to evaluate the effectiveness of artificial intelligence (AI) models in predicting ioCSF. METHODS: Literature records were retrieved on June 13th, 2024, using the relevant key terms without filters in PubMed, Embase, Scopus, and Web of Science. Records were screened according to the eligibility criteria, and the data from the included studies were extracted. The quality assessment was performed using the QUADAS-2 tool. The meta-analysis, sensitivity analysis, and meta-regression were conducted using R software. RESULTS: Our results demonstrate that the AI models achieved a pooled sensitivity of 93.4% (95% CI: 74.8%- 98.6%) and specificity of 91.7% (95% CI: 75%- 97.6%). The subgroup analysis revealed that the pooled sensitivities in ML and DL were 86.2% (95% CI: 83%- 88.8%) and 99% (95% CI: 93%- 99%), respectively (P<0.01). The subgroup analysis demonstrated a pooled specificity of 92.1% (95% CI: 63.1%- 98.7%) for ML and 90.6% (95% CI: 78.2%- 96.3%) for DL models (P= 0.87). The DOR meta-analysis revealed an odds ratio (OR) 114.6 (95% CI: 17.6- 750.9). The SROC curve demonstrated that the overall AUC of the studies was 0.955, which is a considerable performance. CONCLUSION: AI models have demonstrated promising performance for predicting the ioCSF leakage in pituitary surgery and can optimize the treatment strategy.

Monte Carlo Model Validation of 6MV Beam of OMID, the First Iranian Linear Accelerator.

Monte Carlo (MC) techniques are regarded as an accurate method to simulate the dose calculation in radiotherapy for many years. The present paper aims to validate the simulated model of the 6-MV beam of OMID linear accelerator (BEHYAAR Company) by EGSnrc codes system and also investigate the effects of initial electron beam parameters (energy, radial full width at half maximum, and mean angular spread) on dose distributions. For this purpose, the comparison between the calculated and measured percentage depth dose (PDD) and lateral dose profiles was done by gamma index (GI) with 1%-1 mm acceptance criteria. MC model validating was done for 3 cm × 3 cm, 5 cm × 5 cm, 8 cm × 8 cm, 10 cm × 10 cm, and 20 cm × 20 cm field sizes. To study the sensitivity of model to beam parameters, the field size was selected as 10 cm × 10 cm and 30 cm × 30 cm. All lateral dose profiles were obtained at 10 cm. Excellent agreement was achieved with a 99.2% GI passing percentage for PDD curves and at least 93.8% GI for lateral dose profiles for investigated field sizes. Our investigation confirmed that the lateral dose profile severely depends on the considered source parameters in this study. PDD only considerably depends on the initial electron beam energy. Therefore, source parameters should not be specified independently. These results indicate that the current model of OMID 6-MV Linac is well established, and the accuracy of the simulation is high enough to be used in various applications.

The clinical utility of autologous tumor lysate-loaded dendritic cell vaccination for patients with glioma: A systematic review and meta-analysis.

BACKGROUND: Dendritic cell (DC) vaccines show promise for glioma treatment, but optimal use remains uncertain. This meta-analysis examined DC vaccine efficacy and safety for gliomas. METHODS: This systematic review and meta-analysis study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. From the date of inception to October 23, 2023, electronic databases PubMed, Embase, Web of Science, and Scopus have been thoroughly evaluated. RESULTS: A total of 12 studies with 998 patients and a mean age ranging from 40.2 to 56 years were included. Across 12 articles, DC vaccine 6-month overall survival (OS) was 100% [95% confidence interval {95%CI}: 100%-100%]. Respectively, 12-month OS reported 75% [95%CI: 65%-85%] but declined to 32% [95%CI: 20%-43%] for 24-month OS. 6- and 12-month progression-free survival reached 49% [95%CI: 21%-77%] and 19% [95%CI:8%-30%]. Studying radiological outcomes shows that complete response and partial response rates were 13% [95%CI: 17%-42%], and 26% [95%CI: 10%-42%], though stable disease reached 33% [95%CI: 15%-51%], suggesting predominant antineoplastic effects. The progressive disease rate also was 24% [95%CI: 9%-57%]. CONCLUSIONS: In gliomas, DC vaccinations show a temporary efficacy; stability is more prevalent than regression. Impacts favor decreased resistance to early disease. Enhancing efficacy remains critical. Early therapy can be enhanced by appropriate supplementary therapy integration.

Choline chloride and amino acid solutions taste and hydration behavior with experimental thermodynamic properties and COSMO-PC-SAFT calculation.

Aqueous amino acid solutions have been introduced as dietary supplements for both animals and humans. This study investigates the physicochemical properties of the solutions containing amino acids (L-glycine, D,L-alanine, L-proline), choline chloride, and water at temperature range of 288.15 to 318.15 K. The results show that increasing concentrations of amino acids and choline chloride lead to higher solution densities. Analysis of apparent molar volume (Vφ) and apparent molar isentropic compressibility (κφ) reveals that Vφ values increase with choline chloride concentration and temperature, indicating enhanced solute-solvent interactions, while κφ values decrease, suggesting increased solution compression. Thermodynamic analysis using the Redlich-Mayer model and COSMO-based modeling provides insights into molecular interactions. However, COSMO-based parameters show high average relative deviation percentage (ARD %) values, indicating poor predictive performance for the density of these systems. In contrast, the ePC-SAFT equation of state effectively predicts the densities, particularly for L-proline-based solutions, which show very low ARD % values, indicating high accuracy. The ePC-SAFT model also performs reasonably well for L-glycine solutions but shows poorer results for D,L-alanine-based solutions. The study also examines the sweetness and saltiness criteria (ASV and ASIC) of these solutions. The ASV values, which serve as a sweetness criterion, are higher than the ideal range of 0.5 < ASV < 0.7, suggesting an overly sweet taste. The ASIC values follow a similar trend, indicating increased saltiness. To achieve an appropriate grade of sweetness and saltiness, dilution to lower concentrations of the solution is recommended. Furthermore, the use of choline chloride is found to increase salt intake and enhance the taste of salt, which can be beneficial in amino acid supplements used in animal food.

Consumption of a new developed synbiotic yogurt improves oxidative stress status in adults with metabolic syndrome: a randomized controlled clinical trial.

Association between metabolic syndrome (MetS) and oxidative stress has been shown in numerous studies. It has been shown that probiotics could be the effective treatment strategy in improving oxidative stress. This study aimed to determine the effects of a new developed synbiotic yogurt on oxidative stress status in adults with MetS. Forty-four individuals were assigned into two groups and given 300 g of synbiotic yogurt containing Lactobacillus plantarum, Lactobacillus pentosus, and Chloromyces marcosianos yeast or regular yogurt for 12 weeks in this randomized, placebo-controlled clinical trial. Before and after the intervention, biochemical parameters were assessed. Daily consumption of synbiotic yogurt in adults with MetS showed a statistically significant improvement in the level of glutathione peroxidase (p = 0.01) and total oxidant status (p = 0.006) compared to the regular yogurt. Total Antioxidant Capacity and superoxide dismutase levels increased significantly (p = 0.002 and p = 0.02, respectively) in the intervention group compared to the baseline levels. In adults with MetS, daily consumption of the synbiotic yogurt containing native strains of Lactobacillus plantarum, Lactobacillus pentosus, and Chloromyces marcosianos yeast for 12 weeks was associated with improvements in oxidative stress status.Trial registration number: Iranian Registry of Clinical Trials (IRCT20220426054667N1) (18/05/2022).

Efficacy of preladenant in improving motor symptoms in Parkinson's disease: A systematic review and meta-analysis.

Background: Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by dopamine depletion and severe motor impairments. Preladenant, an adenosine A2 receptor antagonist, is an investigational treatment for PD. This systematic review and meta-analysis aimed to critically evaluate the efficacy of Preladenant in improving motor symptoms in patients with PD. Methods: A comprehensive literature search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to March 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) comparing Preladenant with placebo in PD patients were included. The primary outcome was the change in daily ON time without troublesome dyskinesia. Secondary outcomes included the change in daily OFF time and adverse events. The risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Four RCTs with a total of 2097 PD patients were included. Pooled analysis showed that Preladenant could generally increase daily ON time (pooled effect 0.15 and 95 % CI: -0.19-0.48) and reduce daily OFF time (pooled effect -0.04 and 95 % CI: -0.43-0.36) compared to placebo, however it was not significant. The included studies had moderate to high heterogeneity. No significant differences in adverse events were observed between Preladenant and placebo. Conclusion: This meta-analysis suggests that Preladenant may improve motor fluctuations in PD patients by increasing ON time and reducing OFF time. However, the high heterogeneity among studies warrants further large-scale, high-quality RCTs to confirm these findings and establish the long-term safety and efficacy of Preladenant in PD management.

An Updated Comprehensive Review of Plants and Herbal Compounds with Antiasthmatic Effect.

Background: Asthma is a common disease with rising prevalence worldwide, especially in industrialized countries. Current asthma therapy with traditional medicines lacks satisfactory success, hence the patients' search for alternative and complementary treatments for their diseases. Researchers have conducted many studies on plants with antiallergic and antiasthmatic effects in recent decades. Many of these plants are now used in clinics, and searching for their mechanism of action may result in creating new ideas for producing more effective drugs. Purpose: The goal of this review was to provide a compilation of the findings on plants and their active agents with experimentally confirmed antiasthmatic effects. Study Design and Method. A literature search was conducted from 1986 to November 2023 in Scopus, Springer Link, EMBASE, Science Direct, PubMed, Google Scholar, and Web of Science to identify and report the accumulated knowledge on herbs and their compounds that may be effective in asthma treatment. Results: The results revealed that 58 plants and 32 herbal extracted compounds had antiasthmatic activity. Also, 32 plants were shown to have anti-inflammatory and antioxidative effects or may act as bronchodilators and potentially have antiasthmatic effects, which must be investigated in future studies. Conclusion: The ability of herbal medicine to improve asthma symptoms has been confirmed by clinical and preclinical studies, and such compounds may be used as a source for developing new antiasthmatic drugs. Moreover, this review suggests that many bioactive compounds have therapeutic potential against asthma.

Mirtazapine Improves Locomotor Activity and Attenuates Neuropathic Pain Following Spinal Cord Injury in Rats via Neuroinflammation Modulation.

Neuroinflammation-related locomotor deficits and neuropathic pain are expected outcomes of spinal cord injury (SCI). The atypical antidepressant mirtazapine has exhibited potential neuroprotective and anti-inflammatory effects. This research aims to investigate the impacts of mirtazapine on post-SCI neuropathic pain and locomotor recovery, with a particular focus on neuroinflammation. The study utilized 30 male Wistar rats divided into five groups: Sham, SCI with vehicle treatment, and SCI administered with mirtazapine (3, 10, and 30 mg/kg/day, ip, for one week). Locomotor activity was assessed using the Basso, Beattie, and Bresnahan (BBB) scale. Mechanical, thermal, and cold allodynia were assessed using von-Frey filaments, tail flick latency, and the acetone test, respectively. ELISA was utilized to measure cytokines, while Western blotting was used to determine TRPV1 channel, 5-HT2A receptor, NLRP3, and iNOS expression. Histopathological analyses were also examined, including hematoxylin and eosin (H&E) and Luxol fast blue (LFB) staining. Mirtazapine (10 and 30 mg/kg/day) significantly improved locomotor recovery according to BBB score. It attenuated mechanical, thermal, and cold allodynia post-SCI. Moreover, it decreased pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-18, while increasing anti-inflammatory cytokine IL-4 and IL-10. Furthermore, it downregulated iNOS, NLRP3, and TRPV1 expression and upregulated the 5-HT2A receptor. H&E and LFB staining further revealed attenuated tissue damage and decreased demyelination. Our findings suggest that mirtazapine can alleviate neuropathic pain and reinforce locomotor recovery post-SCI by modulating neuroinflammatory responses, NLRP3, iNOS, TRPV1 channel, and 5-HT2A receptor expression.

Cardioprotective effects of GPER agonist in ovariectomized diabetic rats: reversing ER stress and structural changes.

The incidence of diabetic cardiomyopathy (DCM) significantly increases in postmenopausal women, suggesting protective roles of estrogen. Excessive endoplasmic reticulum (ER) stress alters myocardial structure, which plays a crucial role in DCM. The G protein-coupled estrogen receptor (GPER) has been demonstrated to have cardioprotective effects, but it remains unclear whether these effects involve the amelioration of structural changes induced by ER stress. The objective of this study was to determine whether GPER can prevent cardiac structural changes by attenuating ER stress. Female ovariectomized (OVX) rats were divided into three groups: OVX, OVX + T2D, and OVX + T2D + G1. T2D was induced by a high-fat diet, and streptozotocin and G1, a GPER agonist, were administered for 6 weeks. Finally, histological changes of the myocardium were examined and the expression of sarcoplasmic reticulum calcium ATPase (SERCA2α), GRP78 as an ER stress marker, and apoptotic signalings were determined by Western blot. We observed that the induction of T2D resulted in an increased cardiac weight index, left ventricular wall thickness, and myocyte diameter. However, GPER activation reversed these changes. T2D increased cardiac protein levels of GRP78, caspase-12, and Bax, while decreasing levels of SERCA2α and Bcl-2. Nevertheless, GPER activation reduced the expression of GRP78 in OVX + T2D rats. Furthermore, GPER activation significantly reduced cardiac caspase-12 and Bax levels and increased SERCA2α and Bcl-2 expression. In conclusion, our data suggest that GPER activation ameliorates DCM by inhibiting ER stress-induced cardiac structural changes. These findings provide a new potential target for therapeutic intervention and drug discovery specifically tailored for postmenopausal diabetic women.

Extraction optimisation and characterisation of Artocarpus integer peel pectin by malonic acid-based deep eutectic solvents using response surface methodology.

Traditional pectin extraction methods involve strong acids, which are environmentally harmful. This study explores an innovative approach using Malonic Acid (MA)-based Deep Eutectic Solvents (DES) to extract pectin from Artocarpus integer Peel (AIPP), optimised through Response Surface Methodology (RSM). The extracted AIPP-A and AIPP-B from ChCl-MA and ChDHCit-MA DES, respectively, were characterised for yield, pH, solubility, Degree of Esterification (DE), Water and Oil Holding Capacity (WHC and OHC). The experimental values aligned with RSM model predictions, with low standard deviations: 0.7300 for ChCl-MA and 0.1531 for ChDHCit-MA. Optimal extraction conditions for AIPP-A were 3.27 % ChCl-MA, 1.28 h extraction time, 50.44 °C temperature, and a 1:40 g/mL solid-to-liquid ratio. For AIPP-B, the conditions were 4.95 % ChDHCit-MA, 2.04 h extraction time, 79.65 °C temperature, and a 1:50 g/mL solid-to-liquid ratio. ChCl-MA yielded 30.97 % AIPP, which was higher than that of ChDHCit-MA (27.99 %). Both AIPP demonstrated desirable properties such as low pH, high solubility, and significant DE. AIPP-A exhibited a greater DE (58.40 %) compared to AIPP-B (32.4 %) contributed to its lower WHC and higher OHC. In conclusion, RSM-based optimisation of AIPP extraction with DES is effective in producing pectin that is suitable for use as a gelling agent, preservative, and stabiliser in the food industry.

Quizartinib: a new hope in acute myeloid leukemia, an applied comprehensive review.

Acute myeloid leukemia (AML) is caused by a defective precursor leading to malignant clonal expansion, often with FMS-like tyrosine kinase-3 receptor (FLT3) mutations, particularly internal tandem duplication (ITD), which has a poor prognosis. Quizartinib, a second-generation FLT3 inhibitor, has FDA approval for relapsed/refractory AML with FLT3/ITD mutation. It has shown promise in clinical studies since 2013 due to its excellent oral absorption and potent activity on FLT3. This review explores Quizartinib's mechanism of action, efficacy in monotherapy or combination with chemotherapy, drug interactions, adverse events, resistance mechanisms and future research directions.

Discover Quizartinib's journey in AML treatment: from its targeted FLT3 inhibition mechanism to overcoming resistance. Clinical trials show promise, but the battle against side effects continues. #Quizartinib #AML #FLT3resistance #ClinicalTrials.

Insight into the role of integrins and integrins-targeting biomaterials in bone regeneration.

Features of the extracellular matrix, along with biochemical factors, have a momentous impress in making genes on and/or off. The interaction of cells and the extracellular matrix is mediated by integrins. Therefore, these molecules have pivotal roles in regulating cell behaviors. Integrins include a group of molecules with a variety of characteristics that can affect different molecular cascades. Considering the importance of these molecules in tissue regeneration after injury, it is necessary to know well the integrins involved in the process of connecting cells to the extracellular matrix in each tissue.With the increase in life expectancy, bone tissue engineering has received more attention from researchers. Integrins are critical components in osteoblast differentiation, survival, and bone mechanotransduction. During osteogenic differentiation in stem cells, specific integrins facilitate multiple signaling pathways through their cytoplasmic domain, leading to the induction of osteogenic differentiation. Also, due to the importance of using biomaterials in bone tissue engineering, efforts have been made to design and use biomaterials with maximum interaction with integrins. Notably, the use of RGD peptide or fibronectin for surface modification is a well-established and commonly employed approach to manipulate integrin activity.This review article looks into integrins' role in bone development and regeneration. It then goes on to explore the complex mechanisms by which integrins contribute to these processes. In addition, this review discusses the use of natural and synthetic biomaterials that target integrins to promote bone regeneration.

Unlocking daidzein's healing power: Present applications and future possibilities in phytomedicine.

BACKGROUND: Cancer is one of the leading causes of death and a great threat to people around the world. Cancer treatment modalities include surgery, radiotherapy, chemotherapy, radiochemotherapy, hormone therapy, and immunotherapy. The best approach is to use a combination of several types. Among the treatment methods mentioned above, chemotherapy is frequently used, but its activity is hampered by the development of drug resistance and many side effects. In this regard, the use of medicinal plants has been discussed, and in recent decades, the use of isolated phytochemicals came into the focus of interest. By critically evaluating the available evidence and emphasizing the unique perspective offered by this review, we provide insights into the potential of daidzein as a promising therapeutic agent, as well as outline future research directions to optimize its efficacy in clinical settings. PURPOSE: To summarized the therapeutic potential of daidzein, an isoflavone phytoestrogen in the management of several human diseases with the focuses on the current status and future prospects as a therapeutic agent. METHODS: Several search engines, including PubMed, GoogleScholar, and ScienceDirect, were used, with the search terms "daidzein", "daidzein therapeutic potential", or individual effects. The study included all peer-reviewed articles. However, the most recent publications were given priority. RESULTS: Daidzein showed protective effects against malignant diseases such as breast cancer, prostate cancer but also non-malignant diseases such as diabetes, osteoporosis, and cardiovascular diseases. Daidzein activates multiple signaling pathways leading to cell cycle arrest and apoptosis as well as antioxidant and anti-metastatic effects in malignant cells. Moreover, the anticancer effects against different cancer cells were more prominent and discussed in detail. CONCLUSIONS: In short, daidzein represents a promising compound for drug development. The comprehensive potential anticancer activities of daidzein through various molecular mechanisms and its therapeutic/clinical status required further detail studies.

Neurofilament light chain as a promising biomarker for depression diagnosis: a systematic review and meta-analysis.

BACKGROUND: Depression is a prevalent and serious mental health disorder that significantly impacts daily life and functioning. Neurofilament Light chain (NfL), associated with axonal neuronal damage, has been identified as a promising biomarker, potentially aiding in early diagnosis of depression, personalized treatment, and tracking disease progression. This study used meta-analysis to evaluate the potential of plasma NfL as a biomarker for depression patients. METHODS: A systematic search following the PRISMA guidelines was conducted across PubMed, Web of Science, Scopus, and Google Scholar databases to find relevant studies on plasma NfL levels in patients with depression. A random effects model meta-analysis was applied to determine its potential as a biomarker for differentiating patients from controls. RESULTS: Our meta-analysis, based on four articles with six datasets, revealed that plasma NfL levels were notably higher in individuals with depression (228 cases) compared to healthy controls (118 individuals). The weighted mean difference (WMD) was 8.78 (95% CI: 5.28, 12.28; P < 0.01), indicating a significant effect size. Given the diverse confounding factors inherent in the included observational studies, the observed variability can be attributed to these influences. Due to the observed heterogeneity (heterogeneity Chi-Square: 54.91, p < 0.05), we performed a subgroup analysis. Subgroup analyses based on depression type and analysis method consistently supported the association between NfL and depression, strengthening the evidence. CONCLUSION: Our meta-analysis demonstrates that elevated NfL levels may serve as a promising biomarker for diagnosing depressive disorders. Further research on diverse subtypes and longitudinal changes is needed to validate its clinical utility.

A comprehensive investigation of the associations between tensor-based morphometry indices and executive functions, memory, language, and visuospatial abilities in patients in the Alzheimer's disease continuum.

OBJECTIVES: Based on the literature, tensor-based morphometry (TBM) parameters were related to neurocognitive functions such as memory, learning, language ability, and executive functions. The present study aims to evaluate the associations between TBM indices with executive functions, memory, language, and visuospatial abilities and the value of TBM in the clinical diagnosis of Alzheimer's disease (AD) among individuals with Alzheimer's disease continuum and mild cognitive impairment (MCI) from Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: The authors used ADNI-memory (ADNI-MEM), ADNI-executive functions (ADNI-EF), ADNI-language (ADNI-LAN), and ADNI-visuospatial (ADNI-VS) composite scores. TBM parameters, including measure 1, which represents average within a statistically defined region-of-interest inside the temporal lobes and measure 2 which indicates average within an anatomically defined region-of-interest including bilateral temporal lobes were utilized in the current study. Statistical analysis was performed using IBM SPSS Statistics version 26, and Pearson's correlation, Bonferroni's correction, and multiple linear regression were utilized for data analysis. P <0.05 was considered statistically significant. RESULTS: After screening 800 participants, 270 (151 men, 119 women) were selected for a study with TBM scores and cognition-related assessments at 6, 12, and 24 months. Groups included healthy controls (n=53), MCI (n=158), and Alzheimer's Disease (AD) (n=59). TBM indices correlated with cognitive scores in MCI and AD groups but not healthy controls. Changes in TBM indices and cognitive scores were significantly correlated in MCI and AD groups over 24 months. TBM indices were weak predictors of cognitive decline at all time points. CONCLUSIONS: TBM can help physicians diagnose MCI and AD early. However, TBM could not strongly predict cognitive functions decline at all time points.

COVID-19 vaccination anti-cancer impact on the PI3K/AKT signaling pathway in MC4L2 mice models.

The most promising method of containing the COVID-19 pandemic is considered to be vaccination against SARS-CoV-2 infection. However, research on the relationship between vaccination against COVID-19 and cancer has primarily examined induced immunity rather than the disease itself. Considering that breast cancer is the most common cancer among women, the main goal of this study was to examine the impact of the Sinopharm and AstraZeneca vaccination on tumor characteristics such as tumor size, important tumor markers, tumor-infiltrating lymphocytes, metastasis to vital organs, and investigation of the PI3K/AKT signaling pathway, and the expression levels of relevant genes (PTEN, mTOR, AKT, PI3K, GSK3, and FoxO1) of the luminal B (MC4L2) mouse model. The tumor size of the mice was measured and monitored every two days, and after thirty days, the mice were euthanized. Remarkably, after vaccination, all vaccinated mice showed a decrease in the size of their tumor and an increase in the number of lymphocytes that had invaded the tumors. Tumor marker levels (VEGF, Ki-67, MMP-2/9), CD4/CD8 ratio, metastasis to vital organs, hormone receptors (ER, PR, and HER-2), and expression of genes related to the advancement of the PI3K/AKT signaling pathway were lower in vaccinated mice. Our research showed that the COVID-19 vaccine can have an anti-cancer effect by slowing the tumor progression and metastasis.

Strain-specific effects of probiotics on depression and anxiety: a meta-analysis.

INTRODUCTION: Depression and anxiety are pervasive mental health disorders with substantial global burdens. Probiotics, live microorganisms known for their health benefits, have emerged as a potential therapeutic intervention for these conditions. This systematic review and meta-analysis aim to evaluate the strain-specific effects of probiotics on relieving depressive and anxiety symptoms while elucidating underlying mechanisms. METHODS: EMBASE, Cochrane CENTRAL and PubMed/Medline were systematically queried to identify studies released until May 15, 2024. Randomized Controlled Trials (RCTs) that employed standardized assessment tools for depression and anxiety namely Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Depression Anxiety Stress Scales (DASS), or Montgomery-Asberg Depression Rating Scale (MADRS) were included. RESULTS: 12 RCTs involving 707 participants were included. Seven RCTs utilizing the BDI questionnaire demonstrated a significant decrease in depressive symptoms favoring probiotics containing strains such as Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium breve, and Bifidobacterium longum (MD: -2.69, CI95%: -4.22/-1.16, p value: 0.00). Conversely, RCTs using HAMD showed a non-significant reduction in depressive symptoms (MD: -1.40, CI95%: -3.29/0.48, p value: 0.14). RCTs employing DASS and MADRS scales also showed no significant differences. CONCLUSION: This meta-analysis offers valuable insights into the strain-specific effects of probiotics containing Lactobacillus and Bifidobacterium species on depressive and anxiety symptoms. While our findings suggest a significant reduction in depressive symptoms based on the BDI scale favoring probiotics, the lack of significant effects observed on the HAMD, DASS, and MADRS scales underscores the complexity inherent in these conditions. It is imperative to acknowledge the mixed results across different measurement scales, indicating the need for cautious interpretation. Therefore, we advocate for a nuanced understanding of probiotics' impacts on various dimensions of mood, emphasizing the necessity for further research.

Assessing the effectiveness and safety of Patisiran and Vutrisiran in ATTRv amyloidosis with polyneuropathy: a systematic review.

Background: Hereditary transthyretin (ATTRv) amyloidosis, a multifaceted disorder affecting multiple systems, substantially diminishes patients' physical capabilities and overall quality of life. Patisiran and Vutrisiran, two Ribonucleic acid (RNA) interference therapies, target reducing both pathogenic and wild-type transthyretin (TTR) protein levels. This systematic review assesses the effectiveness and safety of these treatments in managing ATTRv. Methods: A comprehensive, thorough literature search across databases including Embase, PubMed, Web of Science, Cochrane Central, and Google Scholar yielded 858 studies. Following removing duplicate and irrelevant articles, 676 distinct studies underwent review. These studies, conducted on a global scale, encompassed a range of methodologies, including clinical trials and indirect treatment comparisons. Results: Ten studies, spanning a total population of 756 patients, were selected for in-depth analysis. Patisiran and Vutrisiran consistently demonstrated significant improvements in primary and secondary endpoints related to neuropathy, quality of life, and cardiac function. Both medications were well-tolerated, with primarily mild to moderate adverse events. Indirect treatment comparison studies indicated Vutrisiran's superiority over Tafamidis in treating ATTRv amyloidosis. Conclusion: This systematic review recommends using Patisiran and Vutrisiran to treat ATTRv amyloidosis. The findings suggest that these RNA interference therapies improve neuropathy, quality of life, and cardiac symptoms. The results indicate sustained benefits over prolonged treatment, with satisfactory safety profiles. However, potential biases, conflicts of interest in the studies, and limited follow-up periods in some trials necessitate cautious interpretation. Future research should address these limitations and provide more robust evidence for the long-term efficacy and safety of Patisiran and Vutrisiran in ATTRv treatment.