👤 Aftab Karimi

Despite the growing interest in cell- and exosome-based therapies for neurological diseases including Alzheimer's disease (AD), there is still a gap in the investigation of more effective treatments in terms of efficacy, safety, and durability of effect. This study aimed to compare the therapeutic potential of astrocyte cells and their derived exosomes (AS-Exos) in restoring cognitive function in a mouse model of AD. AD model was induced by bilateral electrical lesioning of the nucleus basalis of Meynert (NBM). Astrocytes were isolated from neonatal rat brains, and AS-Exos were harvested from astrocyte-conditioned media using an AnaCell extraction kit. Seven days after lesion induction, astrocytes and AS-Exos were stereotaxically injected into the NBM. Four weeks later, behavioral assessments (passive avoidance and locomotor activity), electrophysiological recordings (EEG), and biochemical measurements of hippocampal brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels were performed. AS-Exos were confirmed as cup-shaped vesicles (30-150 nm) expressing the exosomal surface markers CD9, CD63, and CD81. NBM lesions significantly reduced step-through latency (STL), hippocampal BDNF and ACh levels, and disrupted EEG oscillatory patterns. Treatment with AS-Exos markedly improved STL and produced greater increases in hippocampal BDNF and ACh levels compared with AD and AD+saline groups. EEG analysis also revealed enhanced beta, alpha, and gamma power, with the most robust normalization observed in the AS-Exos group. AS-Exos demonstrated superior biochemical and electrophysiological benefits compared with astrocyte transplantation and provided equal or greater improvement in behavioral outcomes. These findings highlight AS-Exos as a promising cell-free therapeutic strategy for alleviating cognitive deficits associated with AD. Show less

Novel therapeutic approaches, such as exosome therapy, have garnered considerable attention for the treatment of central nervous system (CNS)-related disorders. This study aimed to investigate the effect of Neural stem cell-derived exosomes(Exo-NSC) on improving behavioral, molecular, and electrophysiological symptoms. Rats were divided into: control, lesioned groups (Alz, Alz + saline), treatments (Alz + NSC, Alz + Exo-NSC). the nucleus basalis of meynert (NBM) was lesioned using electrical lesion. One week after lesion, saline, NSC, and Exo-NSC were injected into the NBM. Twenty-eight days post-injection, behavioral tests (passive avoidance memory and locomotor activity) and EEG recordings were conducted. Subsequently, hippocampal levels of brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) were measured. NBM lesioning significantly reduced the step-through latency (STL), decreased alpha and gamma wave frequencies, increased theta and delta wave frequencies, and reduced Ach and BDNF levels compared to the control group. The NSC injection resulted in decreased delta wave frequency, increased gamma wave frequency, and elevated BDNF levels. Meanwhile, Exo-NSC injection significantly increased STL, beta and gamma wave frequencies, and levels of ACh and BDNF compared to lesioned groups. Overall, the findings indicate that Exo-NSC injection may be more effective than NSCs in improving passive avoidance memory. This benefit may stem from elevated hippocampal ACh and BDNF levels in the hippocampus. Show less

Major depressive disorder (MDD) remains a leading cause of disability worldwide, and innovative adjunctive strategies are needed to enhance treatment outcomes. This critical appraisal examines a recent pilot study by Decker et al., which evaluated a 10-12 week well-formulated ketogenic diet (WFKD) as an adjunct therapy for college students with MDD. In this uncontrolled cohort (n = 16 completers), mean PHQ-9 and HRSD scores decreased by approximately 69-71% (p < 0.001), accompanied by notable improvements in self-reported wellbeing, cognitive performance, body composition, and metabolic biomarkers (e.g., leptin reduction, BDNF increase). These findings suggest that metabolic interventions may exert clinically meaningful antidepressant effects comparable to conventional therapies. However, as a single-arm study with a small, self-selected sample, causality cannot be established, and placebo effects or concurrent counseling may have contributed to outcomes. The authors appropriately call for larger, randomized controlled trials with longer follow-up and diverse populations to confirm efficacy, explore underlying mechanisms (e.g., neuroinflammation, gut-brain axis modulation), and optimize implementation. If validated, integrating dietary strategies into psychiatric and college counseling programs could offer a low-risk, holistic approach to improving mental health outcomes. Show less

Depression is a widespread neuropsychiatric disorder that significantly impacts emotional and cognitive function. Antidepressant medications are frequently accompanied by various adverse effects. C-phycocyanin has been previously shown to exert potent anti-inflammatory, and neuroprotective properties. Therefore, this study evaluated the therapeutic effects of C-phycocyanin against anxiety and depressive-like behaviors, and memory dysfunction in an animal model of chronic unpredictable mild stress (CUMS)-induced depression and explored the underlying mechanisms. Rats were daily exposed for six weeks to CUMS, during which phycocyanin (100 mg/kg, orally) was administered in the final three weeks of the study. Following the assessment of anxiety/ depressive-like behaviors, and memory dysfunction by the open field test (OFT), tail suspension test (TST), elevated plus maze (EPM), and passive avoidance test (PAT), rats were euthanized by decapitation. Then, hippocampal TNF-α and IL-1β concentrations, and hippocampal protein expressions (Iba-1, CD86, NF-κβ, CREB, and BDNF) were determined by an ELISA assay, and western blots, respectively. C-phycocyanin significantly decreased immobility time in OFT and TST, increased open arm time in EPM, and step-through latency time in PAT. Furthermore, C-phycocyanin suppressed CUMS-induced the M1 microglia polarization and neuroinflammation by reducing hippocampal TNF-α and IL-1β concentrations, and the protein expression of Iba-1, CD86, and NF-κβ in the hippocampus of CUMS-exposed rats. It also increased the hippocampal protein expression of CREB and BDNF. C-phycocyanin improved CUMS-induced anxiety and depressive-like behaviors, and memory dysfunction, which could be explained, at least in part, by inhibition of M1 microglial polarization and neuroinflammation, and enhancement of CREB/BDNF signaling. Show less

Encapsulation of Lactiplantibacillus plantarum (L. plantarum) ZGP-Lpl.19 in alginate-pectin-chitosan microcapsules significantly improved its survival under simulated gastrointestinal conditions and attenuated Shigella flexneri (S. flexneri) growth and pathogenicity through downregulation of the mdoH and IcsA virulence genes. Microencapsulation was achieved via extrusion using a polysaccharide blend, yielding an encapsulation efficiency of 98.44%. Structural integrity of the microcapsules was confirmed by scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). Encapsulation markedly enhanced probiotic survivability, with viable counts of 5.37 log CFU/mL after 60 min in gastric fluid and 120 min in intestinal fluid, compared with 2.25 log CFU/mL for free cells. Both encapsulated and free L. plantarum ZGP-Lpl.19 demonstrated potent antimicrobial activity against S. flexneri ATCC 12022, with comparable antimicrobial metabolite production. The minimum inhibitory concentration (MIC) of cell-free supernatants from both forms was 1/8 of the original concentration. Importantly, real-time PCR analysis confirmed that both encapsulated and free cells significantly downregulated mdoH and IcsA expression. Overall, these findings demonstrate that alginate-pectin-chitosan microencapsulation provides effective protection for L. plantarum and enhances its functional delivery, positioning encapsulated L. plantarum as a promising therapeutic strategy to mitigate S. flexneri infections. Show less

Recent studies suggest a link between dietary fat quality and obesity. Genetic risk scores (GRS) can predict obesity risk based on genetic factors. This study investigates how GRS and fatty acid quality affect visceral adiposity index (VAI) and body adiposity index (BAI) in overweight and obese women. In this study, 278 overweight and obese women (aged 18-58) participated. We have used a comprehensive food frequency questionnaire (FFQ) to evaluate dietary intake and the fatty acids quality indexes. We have employed standard methods to measure biochemical factors, anthropometrics, and physical activity levels. Finally, the GRS was created by combining three SNPs [CAV-1 (rs3807992), Cry-1 (rs2287161), and MC4R (rs17782313)]. The study found that there was no significant association between the quality of fat intake (as measured by CSI score and N6/N3 score) and VAI or BAI in both crude (B = 70.70, SE = 35.14, CI:1.81-139.55, P = 0.04) and adjusted models (B = 93.67, SE = 39.28, CI:16.68-17.68, P = 0.01). CSI provides information on cholesterol and saturated fats. However, there was a notable interaction between the GRS and the N6/N3 score on VAI, suggesting that obese women with high obesity-related SNPs who consumed foods with a higher ratio of N6/N3 fatty acids tended to have an increased VAI. This study shows; that eating more food sources containing a higher ratio of N6/N3 may be the reason for the increase in VAI in obese women who have high obesity-related SNPs and emphasizes the matter of personalized nutrition in obesity issues. Show less

Camels are increasingly recognized for their potential to meet future nutritional and medical needs due to their unique qualities. This study aims to advance our understanding of the genetic basis of body size in dromedaries by employing confirmatory factor analysis (CFA) and genome-wide association studies (GWAS). We used phenotypic data from 9 body measurements of 96 Iranian male camels to develop a latent variable model for body size. The CFA model demonstrated excellent fit (CFI = 0.99, TLI = 0.99, RMSEA = 0.05, SRMR = 0.02), confirming that the selected biometric traits effectively capture the body size latent variable. Subsequent GWAS, utilizing 14,522 SNPs, identified 13 significant SNPs associated with body size across several chromosomes. The candidate genes linked to these SNPs, including Show less

Borderline Personality Disorder (BPD) is a complex and heterogeneous condition characterized by diverse patterns of emotional, interpersonal, behavioral, and identity-related dysfunctions. This study employed both variable-centered and person-centered approaches to examine the relationship between specific BPD domains and key pretreatment client characteristics. A total of 801 combined sample of university students (n = 513, Mean age = 25.30, SD = 6.74, 39.80 % male) and psychiatric outpatients (n = 288, Mean age = 34.96, SD = 8.92, 38.20 % male) completed the Five Factor Borderline Inventory-Short Form (FFBI-SF) alongside measures of defense mechanisms, insight, interpersonal problems, and attachment styles. Confirmatory factor analysis supported the a priori four-factor structure of the FFBI-SF which included Affective Dysregulation, Interpersonal Difficulties, Behavioral Dysregulation, and Identity Problems domains. Variable-centered analyses revealed that these domains showed distinct patterns of associations with client variables. Furthermore, latent profile analysis (LPA) identified five distinct profiles based on FFBI-SF domain scores, which showed clinically important differences in pretreatment client variables, including defense mechanisms, insight, interpersonal problems, and attachment patterns. Overall, findings highlight the importance of integrating variable- and person-centered approaches to understanding BPD as a multidimensional construct. Also, recognizing domain-specific patterns and subgroup differences can support the development of more individualized and clinically responsive interventions. Show less

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects the elderly population globally and there is an urgent demand for developing novel anti-AD agents. In this study, a new series of indole-isoxazole carbohydrazides were designed and synthesized. The structure of all compounds was elucidated using spectroscopic methods including FTIR, Show less

Renal transplantation stands as the sole remedy for individuals afflicted with end-stage renal diseases, and safeguarding them from transplant rejection represents a vital, life-preserving endeavor posttransplantation. In this context, the impact of cytokines, notably IL-27, assumes a critical role in managing immune responses aimed at countering rejection. Consequently, this investigation endeavors to explore the precise function of IL-27 and its associated cytokines in the context of kidney transplant rejection. The study involved the acquisition of blood samples from a cohort of participants, consisting of 61 individuals who had undergone kidney transplantation (comprising 32 nonrejected patients and 29 rejected patients), and 33 healthy controls. The expression levels of specific genes were examined using SYBR Green Real-time PCR. Additionally, the evaluation encompassed the estimation of the ROC curve, the assessment of the relationship between certain blood factors, and the construction of protein-protein interaction networks for the genes under investigation. Significant statistical differences in gene expression levels were observed between the rejected group and healthy controls, encompassing all the genes examined, except for TLR3 and TLR4 genes. Moreover, the analysis of the Area Under the Curve (AUC) revealed that IL-27, IL-27R, TNF-α, and TLR4 exhibited greater significance in discriminating between the two patient groups. These findings highlight the potential importance of IL-27, IL-27R, TNF-α, and TLR4 as key factors for distinguishing between individuals in the rejected group and those in the healthy control group. In the context of kidney rejections occurring within the specific timeframe of 2 weeks to 2 months post-transplantation, it is crucial to emphasize the significance of cytokines mRNA level, including IL-27, IL-27R, TNF-α, and TLR4, in elucidating and discerning the diverse immune system responses. The comprehensive examination of these cytokines' mRNA level assumes considerable importance in understanding the intricate mechanisms underlying kidney rejection processes during this critical period. Show less

For more than eight decades, cardiovascular disease (CVD) has remained the leading cause of death in the world. CVD risk factors are multifaceted, with genetics and lifestyle both playing a role. The aim of this study was to investigate the association between a genetic profile risk score for obesity GRS and cardio-metabolic risk factors in overweight and obese women. The current cross-sectional study was conducted on 391 overweight and obese women. The genetic risk score was created by combining three single nucleotide polymorphisms [MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1 (rs2287161)]. Anthropometric measurements, blood pressure, and some blood parameters were measured by standard protocols. A significant association between the GRS and some of cardiometabolic risk factors variables such as body mass index (β = 0. 49, 95%CI = 0.22 to 0.76, p < 0.001), waist circumference (β = 0. 86, 95%CI = 0.18 to 1.54, p = 0.01), body fat mass (β = 0. 82, 95%CI = 0.25 to 1.39, p = 0.005), %body fat (β = 0. 44, 95%CI = 0.06 to 0.82, p = 0.02), and hs-CRP (β = 0.46, 95% CI = 0.14 to 0.78, p = 0.005) was observed in crude model. After adjustment for confounding factors (age, BMI, and physical activity), a significant positive association was observed between BMI (p = 0.004), WC (p = 0.02), body fat mass (p = 0.01), %BF (p = 0.01), hs-CRP (p = 0.009), and GRS. In addition, we discovered a significant negative association between the GRS and BMC (= -0.02, 95%CI = -0.05 to -0.001, p = 0.04). But other variables did not show any significant association with GRS among obese and overweight women. We found a significant positive association between GRS, including MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1 (rs2287161) and cardiometabolic risk factors among overweight and obese Iranian women. Show less

Congestive heart failure is a complex multifactorial syndrome due to tissue hypoperfusion that is affected by some factors like inflammatory cytokines. In our study, we investigated the exact gene expression of three inflammatory cytokines in ischemic and idiopathic cardiomyopathy patients. From 49 studied recipients in the ischemic group, 23 (46.9%) were male and from 40 studied recipients in the idiopathic dilated cardiomyopathy group, 19 (47.5%) were male. For the quantitative analysis of interleukin (IL)-1, IL-27, and tumor necrosis factor (TNF)-α messenger RNAs expression level, the SYBR Green real-time polymerase chain reaction method was performed using SYBRPremix Ex TaqTM II (Tli RNaseH Plus; Takara) and designed primers specific for each gene in an iQ5 thermocycler (BioRad Laboratories) according to the manufacturer's instructions. Our results showed that the expression level of IL-1 and TNF-α were significantly higher in the ischemic patients compared to healthy controls ( Although we would introduce IL-1, IL-27, and TNF-α as effective inflammatory cytokines on myocardial functions in ischemic and idiopathic cardiomyopathy patients, there is not any difference between these two groups in gene expression of three main inflammatory cytokines. Show less

Different cellular mechanisms contribute to osteocyte development. And while critical roles for members of the zinc finger protein SNAI family (SNAIs) have been discussed in cancer-related models, there are few reviews summarizing their importance for chondrocyte-to-osteocyte development. To help fill this gap, we review the roles of SNAIs in the development of mature osteocytes from chondrocytes, including the regulation of chondro- and osteogenesis through different signaling pathways and in programmed cell death. We also discuss how epigenetic factors-including DNA methylation, histone methylation and acetylation, and noncoding RNAs-contribute differently to both chondrocyte and osteocyte development. To better grasp the important roles of SNAIs in bone development, we also review genotype-phenotype correlations in different animal models. We end with comments about the possible importance of the SNAI family in cartilage/bone development and the potential applications for therapeutic goals. Show less

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic subtype of esophageal cancer worldwide. Measurements of circulating inflammation-related biomarkers may inform etiology or provide noninvasive signatures for early diagnosis. We therefore examined levels of inflammation molecules for associations with ESCC risk. Using a case-cohort study designed within the Japan Public Health Center-based Prospective Study, we measured baseline plasma levels of 92 biomarkers using a multiplex assay in a subcohort of 410 randomly selected participants and 66 participants with incident ESCC (including four cases that occurred in the subcohort). ESCC hazard ratios (HRs) were calculated for 2-4 quantiles of each biomarker by Cox proportional hazards regression models with age as the time metric, adjusted for sex, smoking and alcohol use. Twenty analytes were undetectable in nearly all samples. Of the remaining 72, 12 biomarkers (FGF19, ST1A1, STAMBP, AXIN1, CASP8, NT3, CD6, CDCP1, CD5, SLAMF1, OPG and CSF1) were associated with increased ESCC risk (p Show less

Cytokines have regulatory crosstalk with CMV infection leading to manage of post-liver transplantation virus-related outcomes. To investigate the link between IL-21, IL-23 and IL-27 mRNA and protein level with active CMV infection, which was evaluated in reactivated and non-reactivated liver transplant recipients. Two groups of liver transplant recipients were enrolled in this study-54 without and 15 with active CMV infection. 3 EDTA-treated blood samples were taken on day 1, 4, and 7 post-liver transplantation. Plasma and buffy coats of all samples were separated. All samples were analyzed for CMV reactivation using antigenemia technique. The separated plasma of positive samples was used for viral DNA extraction and protein evaluation. For evaluating the mRNA expression level by real-time PCR, RNA extraction and cDNA synthesis were done for all samples. Also, the protein level of studied genes was estimated by ELISA. The expression level of IL-21, IL-23A and IL-27A cytokine genes was increased in CMV reactivated liver transplant recipients in comparison with CMV non-reactivated ones; IL-27A expression pattern was significant (p=0.001) at all sampling times. IL-21 significantly increased on the 2 Elevation in the expression level of IL-21, IL-23A and IL-27A mRNA and protein level in CMV reactivated patients emphasized on the antiviral role of these cytokines in CMV reactivated liver transplant recipients. Show less