Auraptene inhibits migration, invasion and metastatic behavior of human malignant glioblastoma cells: An in vitro and in silico study.

Objective: The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells. Materials and Methods: To test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot experiments were conducted. Results: At sublethal concentrations of 12.5 and 25 µg/ml, auraptene exhibited a significant reduction in cell invasion and migration of U87 cells, as assessed using scratch wound healing and Transwell tests, respectively. The qRT-PCR and zymography experiments demonstrated a significant decrease in both mRNA expression and activities of MMP-2 and MMP-9 following auraptene treatment. Western blot analysis also showed that MMP-2 protein level and phosphorylation of metastasis-related proteins (p-JNK and p-mTOR) decreased in auraptene-treated cells. Molecular docking studies consistently demonstrated that auraptene exhibits a significant affinity towards MMP-2/-9, the ATP binding site of mTOR and JNK1/2/3. Conclusion: Auraptene inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities.

Advancements in Curcumin-Loaded PLGA Nanoparticle Delivery Systems: Progressive Strategies in Cancer Therapy.

Cancer is a leading cause of death worldwide, and imposes a substantial socioeconomic burden with little impact especially on aggressive types of cancer. Conventional therapies have many serious side effects including generalized systemic toxicity which limits their long-term use. Tumor resistance and recurrence is another main problem associated with conventional therapy. Purified or extracted natural products have been investigated as cost-effective cancer chemoprotective agents with the potential to reverse or delaying carcinogenesis. Curcumin (CUR) as a natural polyphenolic component, exhibits many pharmacological activities such as anti-cancer, anti-inflammatory, anti-microbial, activity against neurodegenerative diseases including Alzheimer, antidiabetic activities (type II diabetes), anticoagulant properties, wound healing effects in both preclinical and clinical studies. Despite these effective protective properties, CUR has several limitations, including poor aqueous solubility, low bioavailability, chemical instability, rapid metabolism and a short half-life time. To overcome the pharmaceutical problems associated with free CUR, novel nanomedicine strategies (including polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs) have been developed. These formulations have the potential to improve the therapeutic efficacy of curcuminoids. In this review, we comprehensively summarize and discuss recent in vitro and in vivo studies to explore the pharmaceutical significance and clinical benefits of PLGA-NPs delivery system to improve the efficacy of CUR in the treatment of cancer.

Roselle (Hibiscus sabdariffa L.) extract as an adjunct to valsartan in patients with mild chronic kidney disease: A double-blind randomized controlled clinical trial.

Objective: The objective of this study was to evaluate the effectiveness of Hibiscus sabdariffa L. extract (HS) as an adjunct to valsartan in the treatment of high blood pressure in patients with mild chronic kidney disease (CKD). Materials and Methods: This trial was conducted in Gorgan, Iran. Seventy-two participants with CKD and high blood pressure were randomly assigned to either the HS group, receiving a 350 mg pill every 12 hr for 90 days along with 40 mg of valsartan every 12 hr, or the control group (40 mg valsartan + 12.5 mg hydrochlorothiazide). The primary objective was to assess the improvement of hypertension, while secondary objectives included the evaluation of proteinuria, albuminuria, kidney function, lipid profile, and electrolyte levels. Molecular docking analysis was performed to examine the mechanisms of action of the isolated components of HS. Results: Out of 80 initial participants, 72 were included in the analysis. Both groups showed a significant reduction in blood pressure (p<0.001). The HS group demonstrated a statistically significant decrease in lipid profile (p<0.001). There were no statistically significant differences between the groups regarding the reduction of renal markers. Molecular docking analysis revealed that the compounds present in HS, particularly its anthocyanins and flavonoids, exhibited greater angiotensin-converting enzyme (ACE) inhibitory potential than hydrochlorothiazide in both domains. Moreover, the compounds met the criteria for drug likeness and Lipinski rules. Conclusion: Adjunctive therapy with HS showed promising results in reducing hypertension and improving lipid profile in patients with CKD.

Effects of cinnamon on anthropometric indices and headache-related disability of patients with migraine: A randomized double-blind placebo-controlled trial.

Objective: Increased body mass index (BMI) seems to be a risk factor for migraine attacks. Cinnamon has anti-inflammatory, neuroprotective, and anti-obesity effects. This study aimed to assess the effects of cinnamon on anthropometric indices and headache-related disability of patients with migraine. Materials and Methods: This study was conducted as a randomized, double-blind, placebo-controlled trial involving 50 migraine patients. Patients were randomized to receive either 600 mg cinnamon powder or placebo capsules for two months. Height, body weight (BW), waist circumference (WC), and hip circumference (HC) were measured.Furthermore, Minimal or Infrequent Disability (MIDAS) and Headache Daily Result (HDR) Questionnaires were recorded. Results: At the end of the treatment period, BW and BMI did not change in the intervention group; however, both factors were significantly increased in the placebo group (p=0.001). The change of WC, HDR and MIDAS was significantly different between the intervention and placebo groups (p<0.001). Furthermore, HC and WHR significantly decreased (p=0.001). Conclusion: Cinnamon seems to have beneficial effects on anthropometric indices and headache disability of migraine patients.

Recent advances in gene delivery nanoplatforms based on spherical nucleic acids.

Gene therapy is a therapeutic option for mitigating diseases that do not respond well to pharmacological therapy. This type of therapy allows for correcting altered and defective genes by transferring nucleic acids to target cells. Notably, achieving a desirable outcome is possible by successfully delivering genetic materials into the cell. In-vivo gene transfer strategies use two major classes of vectors, namely viral and nonviral. Both of these systems have distinct pros and cons, and the choice of a delivery system depends on therapeutic objectives and other considerations. Safe and efficient gene transfer is the main feature of any delivery system. Spherical nucleic acids (SNAs) are nanotechnology-based gene delivery systems (i.e., non-viral vectors). They are three-dimensional structures consisting of a hollow or solid spherical core nanoparticle that is functionalized with a dense and highly organized layer of oligonucleotides. The unique structural features of SNAs confer them a high potency in internalization into various types of tissue and cells, a high stability against nucleases, and efficay in penetrating through various biological barriers (such as the skin, blood-brain barrier, and blood-tumor barrier). SNAs also show negligible toxicity and trigger minimal immune response reactions. During the last two decades, all these favorable physicochemical and biological attributes have made them attractive vehicles for drug and nucleic acid delivery. This article discusses the unique structural properties, types of SNAs, and also optimization mechanisms of SNAs. We also focus on recent advances in the synthesis of gene delivery nanoplatforms based on the SNAs.

Targeting the Akt signaling pathway: Exploiting curcumin's anticancer potential.

Cancer is recognized as one of the leading causes of death worldwide. In recent years, advancements in early detection and expanding treatment options have contributed to a decrease in mortality rates. However, the emergence of drug-resistant cancers necessitates the exploration of innovative and more effective drugs. The Akt kinases play a central role in various signaling pathways that regulate crucial cellular processes, including cell growth, proliferation, survival, angiogenesis, and glucose metabolism. Due to frequent disruptions of the Akt signaling pathway in numerous human cancers and its broad biological implications, targeting this pathway has become a key focus in combating tumor aggressiveness and a promising avenue for therapeutic intervention. Curcumin, a compound found in turmeric, has been extensively studied for its potential as an anti-cancer agent. It demonstrates inhibitory effects on cancer initiation, progression, and metastasis by influencing various processes involved in tumor growth and development. These effects are achieved through negative regulation of transcription factors, growth factors, cytokines, protein kinases, and other oncogenic molecules. This review aims to explore curcumin's anticancer activity against different types of cancer mediated via the PI3K/Akt signaling pathway, as well as its practical applications in treatment.

Differential expression of long non-coding RNAs in colon cancer: Insights from transcriptomic analysis.

BACKGROUND: Colon Cancer (CC) incidence has sharply grown in recent years. Long non-coding RNAs (lncRNA) are produced by a group of non-protein-coding genes, and have important functions in controlling gene expression and impacting the biological features of various malignancies including CC. METHODS: Our research focused on examining the function of lncRNAs in the development of colon cancer. To this end, we selected and analyzed a dataset (GSE104836) from the GEO database, which contained information about the expression of mRNAs and lncRNAs in both colon cancer tissues and normal adjacent paired tumor tissues. The DESeq2 R package in Bioconductor was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) that showed differences in expression levels. Next, by literature review of previous studies, we chose two lncRNAs (FENDRR and LINC00092) for additional studies. To validate our findings, a series of tests were performed on a total of 31 tumor tissues and normal paired adjacent tumor tissues. The lncRNA expression levels were assessed in tumor tissues as well as in surrounding normal tumor tissues. RESULTS: The data confirmed that just two particular lncRNAs, FENDRR and LINC00092, had considerably decreased expression levels throughout all stages of cancer. In addition, the survival assay was conducted using the GEPIA2 software, revealing that a reduced expression of FENDRR is correlated with a reduced overall survival. Furthermore, our investigation using receiver operating characteristic (ROC) methodology revealed that these two lncRNAs had significant discriminatory ability between colon cancer and normal tissues. To determine the cause of the decrease in the activity of these two long non-coding RNAs (lncRNAs), we used methylation-specific PCR (MSP) to examine the methylation pattern of their promoter regions. Our investigation revealed hypermethylation in the promoter regions of FENDRR and LINC00092 within tumor tissues compared to normal adjacent tumor tissues. CONCLUSION: Taken together, our findings revealed the lncRNAs signatures as potential therapeutic targets and molecular diagnostic biomarkers in colon cancer. Furthermore, the evidence provided substantiates the important role of promoter methylation in regulating the expression levels for both of these lncRNAs.

The clinical prognostic significance of miR-140-5p expression in patients with cancer: A Meta and Bioinformatic analysis.

The prognostic value of microRNA-140-5p (miR-140-5p) expression in cancer patients has been investigated, but with inconsistent results. This meta-analysis aims to determine the prognostic significance of miR-140-5p expression in patients with various malignancies. A comprehensive literature search was conducted using PubMed, Web of Science, ProQuest, Cochrane, and Google Scholar to identify relevant studies published before June 2023. Pooled hazard ratios (HR) and odds ratios (OR) with 95 % confidence intervals (CI) were calculated to assess the prognostic importance and clinicopathological features of miR-140-5p in overall survival (OS) and disease-free survival (DFS) of cancer patients, respectively. The CancerMIRNome database and other OS analysis webservers were utilized to explore the prognostic value and expression profile of miR-140-5p. A total of 17 studies were included in the final analysis. The results demonstrated that decreased miR-140-5p expression was significantly associated with inferior OS (pooled HR 0.63; 95 % CI, 0.51-0.79; p < 0.001) and DFS (pooled HR 0.40; 95 % CI, 0.25-0.64; p < 0.001). Pooled ORs indicated a significant correlation between reduced miR-140-5p expression and positive lymph node metastasis (LNM; OR = 3.42; 95 % CI, 2.36-4.94; p < 0.001), advanced tumor stage (OR = 2.80; 95 % CI, 2.07-3.78; p < 0.001), and positive distant metastasis (DM; OR = 10.81; 95 % CI, 3.31-35.30; p < 0.001). No significant associations were observed between miR-140-5p expression and gender (OR = 0.94; 95 % CI, 0.70-1.28; p = 0.70), age (OR = 1.31; 95 % CI, 0.99-1.74; p = 0.06), tumor size (OR = 1.55; 95 % CI, 0.77-3.10; p = 0.22), and histological grade (OR = 1.20; 95 % CI, 0.46-3.10; p = 0.71). Subgroup analyses revealed that decreased miR-140-5p expression was associated with shorter OS in subgroups based on sample size (<100 or >100), tumor origin (GI or non-GI), and cancer type (GC/CRC). Bioinformatic analysis supported the finding that miR-140-5p was downregulated in most tumor tissues, and its reduced expression was linked to poor prognosis in patients with multiple malignancies. The prognostic significance of miR-140-5p in predicting reduced OS and DFS suggests that measuring miR-140-5p expression levels before treatment could serve as a valuable biomarker for identifying cancer patients with an unfavorable prognosis and improving clinical management.

The effect of probiotic consumption on lipid profile, glycemic index, inflammatory markers, and liver function in NAFLD patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND-AIM: Non-alcoholic fatty liver disease (NAFLD1) is the most frequent chronic liver disorder worldwide. Currently, no pharmacological treatment has been approved for NAFLD. Probiotics have been suggested as a potential therapy for NAFLD. The aim of this systematic review and meta-analysis was to assess the impact of probiotic intake on liver tests, lipids, glycemic parameters and inflammatory markers in NAFLD patients. METHODS: We searched electronic databases using related terms. Meta-analysis was performed using random-effects models. Clinical outcomes were presented as standard mean difference (SMD2) with a 95 % confidence interval (CI3). Publication bias and heterogeneity were evaluated in eligible studies. RESULTS: Fifteen randomized clinical trials comprising 899 participants were included in our meta-analysis. Probiotic supplementation improved alanine transaminase [SMD -0.796; 95 % CI (-1.419, -0.172); p = 0.012], Homeostatic Model Assessment for Insulin Resistance (HOMA-IR4) [SMD -0.596; 95 % CI (-1.071, -0.121); p = 0.01] and insulin levels [SMD -1.10; 95 % CI (-2.121, -0.087); p = 0.03]. No significant effects were observed on fasting glucose, hemoglobin A1c, aspartate transaminase, lipid profile, interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: Probiotic intake may improve insulin sensitivity and alanine transaminase in NAFLD patients.

Polymer nanotherapeutics: A promising approach toward microglial inhibition in neurodegenerative diseases.

Nanoparticles (NPs) that target multiple transport mechanisms facilitate targeted delivery of active therapeutic agents to the central nervous system (CNS) and improve therapeutic transport and efficacy across the blood-brain barrier (BBB). CNS nanotherapeutics mostly target neurons and endothelial cells, however, microglial immune cells are the first line of defense against neuronal damage and brain infections. Through triggering release of inflammatory cytokines, chemokines and proteases, microglia can however precipitate neurological damage-a significant factor in neurodegenerative diseases. Thus, microglial inhibitory agents are attracting much attention among those researching and developing novel treatments for neurodegenerative disorders. The most established inhibitors of microglia investigated to date are resveratrol, curcumin, quercetin, and minocycline. Thus, there is great interest in developing novel agents that can bypass or easily cross the BBB. One such approach is the use of modified-nanocarriers as, or for, delivery of, therapeutic agents to the brain and wider CNS. For microglial inhibition, polymeric NPs are the preferred vehicles for choice. Here, we summarize the immunologic and neuroinflammatory role of microglia, established microglia inhibitor agents, challenges of CNS drug delivery, and the nanotherapeutics explored for microglia inhibition to date. We also discuss applications of the currently considered "most useful" polymeric NPs for microglial-inhibitor drug delivery in CNS-related diseases.

Effect of extracorporeal shockwave therapy on plantar fascia thickness in plantar fasciitis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Extracorporeal shockwave therapy (ESWT) has been used as a therapeutic option for plantar fasciitis. The objective was to investigate the effect of ESWT over the plantar fascia thickness. METHODS: MEDLINE, Embase, Web of Science, and SCOPUS databases were searched for randomized controlled trials evaluating the effect of ESWT in patients with plantar fasciitis, comparing ESWT with another treatment. Meta-analysis was conducted using a random-effects model and the generic inverse variance method. Meta-regression and subgroup analyses were also carried out. RESULTS: A total of 14 studies (867 participants) were included. ESWT significantly decreased plantar fascia thickness (weighted mean difference [WMD], -0.21 mm [95% CI -0.39, -0.02]; p = 0.03). No significant improvement in pain was observed (WMD, -0.51 cm [95% CI -1.04, 0.01]; p = 0.06) compared with non-surgical interventions. CONCLUSIONS: Our results suggest that plantar fascia thickness is significantly decreased after ESWT intervention in patients with plantar fasciitis. However, pain relief was not significantly improved compared to other non-surgical interventions.

Nanospheres for curcumin delivery as a precision nanomedicine in cancer therapy.

Cancer is ranked among the top causes of mortality throughout the world. Conventional therapies are associated with toxicity and undesirable side effects, rendering them unsuitable for prolonged use. Additionally, there is a high occurrence of resistance to anticancer drugs and recurrence in certain circumstances. Hence, it is essential to discover potent anticancer drugs that exhibit specificity and minimal unwanted effects. Curcumin, a polyphenol derivative, is present in the turmeric plant (Curcuma longa L.) and has chemopreventive, anticancer, radio-, and chemo-sensitizing activities. Curcumin exerts its anti-tumor effects on cancer cells by modulating the disrupted cell cycle through p53-dependent, p53-independent, and cyclin-dependent mechanisms. This review provides a summary of the formulations of curcumin based on nanospheres, since there is increasing interest in its medicinal usage for treating malignancies and tumors. Nanospheres are composed of a dense polymeric matrix, and have a size ranging from 10 to 200 nm. Lactic acid polymers, glycolic acid polymers, or mixtures of them, together with poly (methyl methacrylate), are primarily used as matrices in nanospheres. Nanospheres are suitable for local, oral, and systemic delivery due to their minuscule particle size. The majority of nanospheres are created using polymers that are both biocompatible and biodegradable. Previous investigations have shown that the use of a nanosphere delivery method can enhance tumor targeting, therapeutic efficacy, and biocompatibility of different anticancer agents. Moreover, these nanospheres can be easily taken up by mammalian cells. This review discusses the many curcumin nanosphere formulations used in cancer treatment.

Effect of Ozone Therapy on Diabetes-related Foot Ulcer Outcomes: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to assess the effectiveness of ozone therapy in treating Diabetes-related Foot Ulcer (DFU) and its outcomes. METHODS: A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and ProQuest databases for published studies evaluating the use of ozone as an adjunct treatment for DFU, from inception to December 21, 2022. The primary outcome measure was the change in wound size after the intervention compared to pretreatment. Secondary outcomes included time to complete ulcer healing, number of healed patients, adverse events, amputation rates, and hospital length of stay. Quantitative data synthesis for the meta-analysis was performed using a random-effects model and generic inverse variance method, while overall heterogeneity analysis was conducted using a fixed-effects model. Interstudy heterogeneity was assessed using the I2 index (<50%) and the Cochrane Q statistic test. Sensitivity analysis was performed using the leave-one-out method. RESULTS: The meta-analysis included 11 studies comprising 960 patients with DFU. The results demonstrated a significant positive effect of ozone therapy on reducing foot ulcer size (Standardized Mean Difference (SMD): -25.84, 95% CI: -51.65 to -0.04, p = 0.05), shortening mean healing time (SMD: -38.59, 95% CI: -51.81 to -25.37, p < 0.001), decreasing hospital length of stay (SMD: -8.75, 95% CI: -14.81 to -2.69, p < 0.001), and reducing amputation rates (Relative Risk (RR): 0.46, 95% CI: 0.30-0.71, p < 0.001), compared to standard treatment. CONCLUSION: This meta-analysis indicates that ozone therapy has additional benefits in expediting complete DFU healing, reducing the amputation rates, and decreasing hospital length of stay, though its effects do not differ from standard treatments for complete ulcer resolution. Further research is needed to address the heterogeneity among studies and to better understand the potential beneficial effects of ozone therapy.

Effect of trehalose on mortality and disease severity in ICU-admitted patients: Protocol for a triple-blind, randomized, placebo-controlled clinical trial.

Background: Improvement in organ failure in intensive care unit (ICU) patients is accompanied by lower mortality rate. A disaccharide, trehalose is a candidate to improve organ failure and survival by autophagy induction and enhancing oxidative stress defense. The aim of this study is to assess the effectiveness of trehalose in improving clinical outcome and reducing mortality in ICU patients. Methods: a triple-blind, randomized, placebo-controlled, two arm, parallel-group, superiority clinical trial will enroll 200 ICU-admitted patients at Imam Reza hospital, Mashhad, Iran. The patients will be randomly allocated to receive either a 100 ml solution of 15 % trehalose or normal saline intravenously. Primary outcomes include ICU mortality and 60-day mortality, while secondary outcomes focus on blood parameters on day 5 and length of hospital/ICU stay. Conclusion: Trehalose has demonstrated beneficial effects in diverse patients; however, no study has evaluated its effect in all ICU-admitted patients. Consequently, this study provides an opportunity to investigate whether trehalose's anti-inflammatory effects, mediated by inducing autophagy and enhancing oxidative stress defense, can play a role in reducing mortality and improving clinical outcomes in the critically ill patients. If successful, trehalose could offer a potential therapeutic approach in the ICU setting.

Prevalence and mechanisms of aminoglycoside resistance among drug-resistant Pseudomonas aeruginosa clinical isolates in Iran.

BACKGROUND: Aminoglycosides have been a cornerstone of the treatment of nosocomial infections caused by Pseudomonas aeruginosa for over 80 years. However, escalating emergence of resistance poses a significant challenge. Therefore, this study aimed to investigate the prevailing patterns of aminoglycoside resistance among clinical isolates of P. aeruginosa in Iran; as well as the underlying resistance mechanisms observed in patients referred to Ardabil hospitals. METHODS: A total of 200 isolates from five hospitals were evaluated. The resistance profiles of P. aeruginosa isolates to tobramycin, amikacin, and netilmicin were determined using the disk diffusion method. The capacity of aminoglycoside-resistant isolates to form biofilms was assessed through a phenotypic assay, and the results were confirmed using the gene amplification technique. The presence of genes associated with aminoglycoside resistance was detected using polymerase chain reaction (PCR). Quantitative reverse transcription PCR (qRT-PCR) was performed to measure the expression levels of genes encoding the MexXY-OprM efflux pump and PhoPQ two-component system (TCS). RESULTS: The prevalence of aminoglycoside-resistant P. aeruginosa isolates was 48%, with 94.7% demonstrating multidrug resistance (MDR). All aminoglycoside-resistant P. aeruginosa strains exhibited biofilm-forming capabilities and harbored all the genes associated with biofilm production. Among the nine genes encoding 16S rRNA methylase and aminoglycoside-modifying enzymes, three genes were detected in these isolates: aac(6')-Ib (85.4%), ant(2'')-Ia (18.7%), and aph(3')-VI (3.1%). Additionally, all aminoglycoside-resistant P. aeruginosa isolates carried mexY and phoP genes, although the expression levels of mexY and phoP were 75% and 87.5%, respectively. CONCLUSION: Given the considerably high prevalence of aminoglycoside-resistant P. aeruginosa strains, urgent measures are warranted to transition towards the use of novel aminoglycosides and to uphold vigilant surveillance of resistance patterns.

Efficacy of statin therapy in reducing epicardial adipose tissue: a systematic review and meta-analysis.

Introduction: Understanding the effect of statins on epicardial adipose tissue (EAT) is important as it may help reduce the negative impact of EAT-derived molecules on the cardiovascular system and consequently on coronary artery disease. Thus, we aimed to perform a systematic review and meta-analysis to assess the impact of statin therapy on EAT. Methods: The study utilized Scopus, PubMed, Embase, and Web of Science to gather relevant studies on the impacts of statins on EAT until September 5th, 2023. The data collected underwent meta-analysis using Comprehensive Meta-Analysis (CMA) V4 software. Results: In the meta-analysis, three studies involving 512 subjects were ultimately incorporated. The findings indicated a significant decrease in EAT after treatment with statins (standardized mean difference (SMD = -0.507, 95% CI: -2.536, 1.521, p = 0.021). Conclusions: Statins appear to exert an additional cardiovascular therapeutic effect by reducing EAT.

The Association between Serum Follistatin-like Proteins and Cardiovascular Diseases: A Systematic Review and Meta-analysis.

BACKGROUND: Follistatin-like proteins (FSTLs) are adipomyokines secreted by adipocytes and myocytes. Previous studies have reported an increase in circulating FSTL1 levels in response to cardiovascular injuries. In this study, we conducted a systematic review and metaanalysis to assess the association between circulating FSTLs and Cardiovascular Diseases (CVDs). METHODS: We performed a comprehensive literature search using PubMed, Web of Science, Scopus, and Embase databases. After screening the articles, we selected eligible studies, extracted relevant data, and calculated the pooled Standardized Mean Difference (SMD). We also conducted a sensitivity analysis to identify sources of heterogeneity and assessed publication bias. RESULTS: Among the 577 articles initially retrieved, we included 5 studies comprising a total of 941 cases with CVDs and 446 controls. All included studies measured FSTL1 levels. The pooled SMD analysis revealed a significant difference in circulating FSTL1 levels between subjects with CVDs and control groups (SMD = 0.853, 95% CI = 0.158-1.548, P = 0.016). Heterogeneity was primarily attributed to a single study that measured FSTL1 levels in heart failure patients with preserved ejection fraction. No publication bias was observed. CONCLUSION: Our findings demonstrate significantly higher levels of FSTL1 in patients with CVD compared to control subjects. This suggests that FSTL1 may have potential as a diagnostic and prognostic biomarker in CVDs. However, further well-designed studies are needed to validate its clinical utility.

Leptin is a potential biomarker of childhood obesity and an indicator of the effectiveness of weight-loss interventions.

Childhood obesity represents a significant public health concern, imposing a substantial burden on the healthcare system. Furthermore, weight-loss programs often exhibit reduced effectiveness in adults who have a history of childhood obesity. Therefore, early intervention against childhood obesity is imperative. Presently, the primary method for diagnosing childhood obesity relies on body mass index (BMI), yet this approach has inherent limitations. Leptin, a satiety hormone produced by adipocytes, holds promise as a superior tool for predicting both childhood and subsequent adulthood obesity. In this review, we elucidate the tools employed for assessing obesity in children, delve into the biological functions of leptin, and examine the factors governing its expression. Additionally, we discuss maternal and infantile leptin levels as predictors of childhood obesity. By exploring the relationship between leptin levels and weight loss, we present leptin as a potential indicator of the effectiveness of obesity interventions.

Stimuli-responsive nanotheranostic systems conjugated with AIEgens for advanced cancer bio-imaging and treatment.

Aggregation-induced emission (AIE) is a unique phenomenon observed in various materials such as organic luminophores, carbon dots (CDs), organic-inorganic nanocomposites, fluorescent dye molecules, and nanoparticles (NPs). These AIE-active materials, or AIEgens, are ideal for balancing multifunctional phototheranostics and energy dissipation. AIE properties can manifest in organic fluorescent probes, rendering them effective for cancer treatment due to their ability to penetrate deeply and provide high therapeutic efficacy. This efficacy is attributed to their high photobleaching thresholds, ability to induce Stokes shifts, and capacity to activate fluorophores. Therefore, the development of innovative AIE-based materials for disease diagnosis and treatment, particularly for cancer, is both important and promising. Recent years have seen successful demonstrations of nanoparticles with AIE properties being used for photodynamic therapy (PDT) and multimodal imaging of tumor cells. These fluorophores have been shown to impact mitochondria and lysosomes, generate reactive oxygen species (ROS), activate the immune system, load and release drugs, and ultimately induce apoptosis in tumor cells. In this review, we examine previous studies on the manufacturing methods and effects of AIEgens on cancer cells, with a theranostic strategy of simultaneous treatment and imaging. We also investigate the factors affecting drug delivery on different cancer cells, including internal stimuli such as pH, ROS, enzymes, and external stimuli like near-infrared (NIR) light and ultrasound waves.

Hope on the Horizon: Promising Therapies for Steatotic Liver Disease.

Steatotic liver disease (SLD) is a highly prevalent chronic liver disease with significant challenges for global health. The pathophysiology of SLD involves an interplay among genetic, endocrine, and metabolic factors. Successful management of SLD entails accurate diagnosis and disease monitoring through noninvasive methods such as advanced imaging techniques and biomarkers. Many emerging pharmacotherapies for SLD are now in the pipeline, which target different pathways like collagen turnover, fibrogenesis, inflammation, and metabolism. The recent approval of resmetirom for noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) has been a milestone in addressing the unmet medical need for an efficacious SLD treatment. Finally, the potential of personalized medicine approaches and interdisciplinary cooperation in improving patient outcomes and reducing disease burden should be strongly pursued. SIGNIFICANCE STATEMENT: The healthcare burden due to steatotic liver disease (SLD) is enormous. This perspective sheds light on the recent advances in understanding the pathophysiology and diagnosis of SLD as well as promising drug development approaches.