Effects of miR-330 restoration on pancreatic cancer cells oncogenesis.

BACKGROUND: Inappropriate expressions of various miRNAs have reported in different human malignancies. Evidence suggested that miR-330 may play as both onco-miR and/or tumor suppressor-miR in different cancers. In the present study, we evaluated effects of miR-330 on proliferation and migration of pancreatic cancer (PC) cells as well as underlying molecular mechanisms. DESIGN: The expression of miR-330 was evaluated in clinical tissue samples of patients with PC. Transfection of the PC cells (PANC-1) by miR-330 was conducted by pCMV vector. The cancer-related genes expression was investigated in mRNA and protein level following transfection of the PC cells. Furthermore, the PC cells viability, invasion, migration, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle profile were investigated after transfection by miR-330. RESULTS: The results indicated that expression of miR-330 downregulated in patients with PC. Stable increase of miR-330 expression after transfection in PC cells reduces viability, mitochondrial membrane potential, invasion, and migration. Further assessments demonstrated that upregulation of miR-330 increases apoptosis and autophagy percentage in the PC cells. Moreover, a cell cycle arrest was observed in G1, Sub-G1, and S phases following transfection of the PC cells. These findings can be explained by modified mRNA and protein expression of apoptosis- and metastasis-related genes. CONCLUSION: Our study suggested that miR-330 acts as a tumor suppressor in PC cells, and revealed that upregulation of miR-330 may provide an effective therapeutic approach for overcoming progression and metastasis in patients with PC.

Design and Production of a Novel Anti-PD-1 Nanobody by CDR Grafting and Site-Directed Mutagenesis Approach.

Programmed cell death protein-1 (PD-1) is a membrane protein expressed on the surface of activated T-cells, B-cells, natural killer cells, dendritic cells, macrophages, and monocytes. Inhibition of the PD-1/PD-L1 interaction by monoclonal antibodies (mAbs) has many therapeutic benefits and has led to a major advance in the treatment of various types of tumors. Due to the large size and immunogenicity of the antibodies (Abs), using small molecules such as nanobodies (nanobodies or VHH) is more appropriate for this purpose. In this research, the complementarity determining regions (CDR) grafting method was used to produce anti-PD-1 nanobody. For producing the grafted anti-PD-1 nanobody, CDRs from the tislelizumab mAb were grafted into the frameworks of a nanobody whose sequence is similar to the tislelizumab mAb. Also, the site-directed mutagenesis method was used to produce two mutated anti-PD-1 nanobodies which increased the affinity of grafted anti-PD-1 nanobodies. Two amino acid substitutions (Tyr97Arg and Tyr102Arg) in the VHH-CDR3 were used to improve grafted nanobody affinity and the binding capacity of the mutated nanobodies. The binding of the anti-PD-1 nanobodies and PD-1 antigen (Ag) was confirmed by Dot blot, western blot, and indirect ELISA analysis. According to the results of these in silico and in vitro studies, the binding between grafted and mutated nanobodies with PD-1 was confirmed. Also, our findings show that site-directed mutagenesis can increase the affinity of nanobodies.

Growth-Associated Protein 43 and Tensor-Based Morphometry Indices in Mild Cognitive Impairment.

Growth-associated protein 43 (GAP-43) is found in the axonal terminal of neurons in the limbic system, which is affected in people with Alzheimer's disease (AD). We assumed GAP-43 may contribute to AD progression and serve as a biomarker. So, in a two-year follow-up study, we assessed GAP-43 changes and whether they are correlated with tensor-based morphometry (TBM) findings in patients with mild cognitive impairment (MCI). We included MCI and cognitively normal (CN) people with available baseline and follow-up cerebrospinal fluid (CSF) GAP-43 and TBM findings from the ADNI database. We assessed the difference between the two groups and correlations in each group at each time point. CSF GAP-43 and TBM measures were similar in the two study groups in all time points, except for the accelerated anatomical region of interest (ROI) of CN subjects that were significantly greater than those of MCI. The only significant correlations with GAP-43 observed were those inverse correlations with accelerated and non-accelerated anatomical ROI in MCI subjects at baseline. Plus, all TBM metrics decreased significantly in all study groups during the follow-up in contrast to CSF GAP-43 levels. Our study revealed significant associations between CSF GAP-43 levels and TBM indices among people of the AD spectrum.

Uncovering the extent of dementia prevalence in Iran: a comprehensive systematic review and meta-analysis.

BACKGROUND: Dementia is one of the major causes of disability and dependency among older people worldwide. The formation of an aging population in Iran can be associated with societal problems, including age-related disorders such as dementia. This study aimed to estimate the prevalence of dementia& Alzheimer disease in adults aged 60 years or older and it's its geographical distribution in Iran. METHODS: A systematic review and meta-analysis study included articles published in both English and Persian languages and utilized various databases including: Google Scholar, PubMed, Web of Science, Magiran, and thesis database of medicine universities up to December 2022. The pooled prevalence was calculated using random effects models. The prevalence was reported separately for different geographical locations and types of area sampling, and age adjustment was performed for the selected studies. All statistical analyses were conducted using metaprop package in STATA version 17. The I2 statistic was applied to assess heterogeneity. RESULTS: The meta-analysis considered nine relevant studies that were carried out up to 2023 in Iran. The study found that the prevalence of dementia in central and east counties was estimated to be 0.14 (95% CI; 0.04-0.31), while in western counties, the prevalence was estimated to be 0.1 (95%CI; 0.01-0.27). The estimated overall crude prevalence of dementia was estimated at 0.14 (95% CI; 0.03-0.31). Estimated prevalence-based health centers sampling and hospital-based studies were 0.02 (95% CI; 0.02-0.03), 0.05 (95% CI 0.06-0.11), respectively. One study used nursing home sampling as the sampling method, and the estimated prevalence was 0.43 (95%CI 0.38-0.49). CONCLUSION: This is the first systematic review and meta-analysis of the prevalence of dementia's disease up to 2023 in Iran. The estimated overall prevalence of dementia is lower than the reported prevalence in European countries and similar to other Asian countries.

Novel and deleterious nucleotide variations in the HAND1 gene probably affect miRNA target sites and protein function in pediatric patients with congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent developmental defect and principal cause of infant mortality and affects cardiac and large blood vessel structures in approximately 1% of live births worldwide. To date, numerous studies have related critical genetic dysfunctions to the pathogenesis of CHDs. However, the genetic basis underlying CHD remains largely unknown. In the present study, we investigated the association of nucleotide variations in coding and noncoding regions of the HAND1 gene with the risk of CHD. The HAND1 gene, encoding a helix-loop-helix transcription factor, is particularly relevant for mechanisms underlying CHD since it plays a significant role in heart development. METHODS AND RESULTS: The genomic DNA of 150 unrelated pediatric patients with CHD was screened by PCR-SSCP and direct sequencing. Four novel and heterozygous missense mutations were identified in the first exon, with three causing amino acid substitutions (p.Val149Met, p.Tyr142His, and p.Leu146Met). In-silico analysis also indicated their deleterious impact on protein structure and function. In addition, we identified five novel nucleotide variants in the 3'UTR region (c.*461, c.*342, c.*529, c.*448, c.*593), potentially altering the target sites of miRNAs. These changes include the loss of certain target sites and the acquisition of new ones. CONCLUSIONS: These findings confirm the phenotypic association between CHDs and HAND1 mutations and can pave the way for developing new preventive and therapeutic strategies.

Chronic Administration of Lisdexamfetamine Induces Apoptosis and Inflammation and Reduces Sperm Quality in Adult Male Rats.

Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time.

Omega-3 supplementation and outcomes of heart failure: A systematic review of clinical trials.

BACKGROUNDS: Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits. METHODS: A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials. RESULTS: The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events. CONCLUSION: Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.

Effect of Dill (Anethum graveolens) Oil on Pruritus and Quality of Life of Hemodialysis Patients: A Randomized Double-Blind Three-Arm Controlled Trial.

Introduction: Anethum graveolens (AG), commonly known as dill, is a plant from the Apiaceae family that has been traditionally used as a skin softener and purifying agent in Persian medicine. In a previous study conducted on male rats, dill was found to have anti-inflammatory effects. The current study aimed to examine the efficacy of topical application of Anethum graveolens oil on pruritus severity, skin dryness, sleep quality, and quality of life in patients undergoing hemodialysis. Methods: In the current clinical trial, the participants were randomly assigned to one of these groups: topical AG preparation, sesame oil, or a control group receiving no treatment. The study was double-blind and placebo-controlled. The topical treatment was applied twice a day for one month to areas of the skin affected by pruritus. The outcome measures included the severity of skin dryness, the Pittsburgh Sleep Quality Index, Duo's Uremic Pruritus Severity Scale, and the Itchy QoL questionnaire. Results: This study involved 106 hemodialysis patients, and after intervention for one month, the medication group had a significantly lower mean score of sleep quality (3.24 ± 2.41) than the placebo (4.54 ± 3.11) and control (5.05 ± 3.21) groups (P=0.032). The mean change in pruritus severity was significantly greater in the medication group (-17.28 ± 8.938) than the placebo (-5.91 ± 5.398) and control (-3.43 ± 3.228) groups (P < 0.001). Moreover, a significant difference was observed in the mean changes in quality of life between the medication, placebo, and control groups, with values of -14.88 ± 7.89, -5.34 ± 4.50, and -1.92 ± 2.86, respectively (P < 0.001). Furthermore, both the medication and placebo groups showed improvement in skin dryness compared to the control group having the values of -1.65 ± 0.91, -1.11 ± 0.79, and -0.38 ± 0.54, respectively (P < 0.001). Conclusion: Topical Anethum graveolens preparation significantly improved the sleep quality and quality of life and reduced skin pruritus and dryness in hemodialysis patients. It could be considered as a simple therapeutic modality to control pruritus in hemodialysis patients. This trial is registered with IRCT2017022032671N1.

Effects of a Spiritual Care Program on Body Image and Resilience in Patients with Second-Degree Burns in Iran.

This research was conducted with the aim of investigating the effect of a spiritual care program (SCP), on the body image and resilience of second-degree burn patients in Iran. In this semi-experimental study, 60 patients with second-degree burns were selected in the Tehran Mottahari Burns Hospital, Iran in 2022. These patients were divided through random allocation into two intervention and control groups. The patients of both groups filled out Beck's self-esteem Test (BSCT) and Connor-Davidson Resilience Scale (CD-RISC) before, immediately, and 3 months after the intervention. In the intervention group, SCP was performed for eight sessions over two weeks. Firstly, the 4D Model of Spiritual Health and Well-Being was examined, then two one-hour sessions were held with each patient about each dimension, with a total of four dimensions including eight sessions, in which these dimensions were examined and discussed. There was no difference in the score of body image (P = 0.326) and resilience (P = 0.597) before intervention in the control and intervention groups. However, the mean of body image score in the intervention group immediately (109.56 ± 4.86) and 3 months after (109.16 ± 6.06) the intervention was significant, respectively. Also, the mean of resilience score in the intervention group was significant immediately (85.86 ± 6.78) and 3 months after the intervention (85.73 ± 6.27). It is suggested for healthcare providers to use the SCPs to reduce the recovery time of burned patients and reduce complications and treatment costs.

Association of Patient Satisfaction with Cataract Grading in Five Types of Multifocal IOLs.

INTRODUCTION: This study investigated patient satisfaction levels in five premium intraocular lenses (IOLs). A secondary aim was to determine whether patient satisfaction was associated with the cataract grade before lens surgery. METHODS: In this multicenter prospective comparative study, 164 patients from diverse backgrounds underwent cataract surgery and were assigned for identical bilateral implantation of multifocal IOLs. In addition to visual performance, quality of life was measured using the National Eye Institute Refractive Error Quality Of Life Instrument (NEI-RQL 42) scoring questionnaire. The Sirius Scheimpflug Analyzer was used to evaluate the posterior cornea and aberrations. Finally, the association of patient satisfaction reports with the Pentacam Cataract Grading Scale (PCGS) and Lens Opacities Classification System (LOCS III) was evaluated. RESULTS: A considerable subjective improvement was observed in uncorrected far, near (40 cm), and intermediate (60 cm) visual acuity in the five groups (P values < 0.001). A significant difference was observed in mesopic and photopic contrast sensitivity between Symfony, Trinova, and AT LISA at the spatial frequency of 12 cycles per degree, favoring Symfony (P < 0.001). PanOptix users had considerably lower mean coma values (P < 0.001), while AT LISA users had lower mean spherical aberrations (P = 0.009) compared to the other groups. No additional safety concerns relating to IOLs were recorded. Mean satisfaction had a high correlation with LOCS and Pentacam Nuclear Staging (PNS) in each lens group, e.g., correlation coefficient and P value for AT LISA were respectively r = 0.99, P < 0.001 and r = 0.97, P = 0.004. CONCLUSION: Despite discrepancies between groups of lenses, most patients who received multifocal IOLs reported satisfaction at more than 3 years after the initial operation. A growing number of patients with cataracts are seeking spectacle-free vision with presbyopia-correcting IOLs. Hence, the high satisfaction rate among patients with cataract could indicate the value of offering a wider range of available lenses.

Propolis as an adjunctive therapy for treatment of uncomplicated cystitis in women: A randomized double-blind placebo-controlled trial.

The current research is designed to investigate the effect of propolis supplementation on the clinical manifestations in women suffering from uncomplicated cystitis. In this randomized double-blind, placebo-controlled trial, 120 women with uncomplicated cystitis were selected and randomly assigned into two groups to receive two 500 mg capsules of propolis or placebo daily for 7 days along with ciprofloxacin (250 mg). Clinical symptoms including hematuria, urinary frequency, dysuria, suprapubic pain, and urgency, as well as bacteriuria, were assessed before and after the intervention. After supplementation, participants in the intervention group had significantly fewer days of urinary frequency (p < 0.001), dysuria (p = 0.005), and urgency (p = 0.03). However, there was no significant difference between the two groups regarding hematuria and suprapubic pain (p > 0.05). Furthermore, the severity of bacteriuria decreased significantly in both groups. In conclusion, it seems that propolis supplementation in women with uncomplicated cystitis could improve urinary frequency, dysuria, and urgency. However, further clinical trials should be conducted to fully understand the effects of propolis in women suffering from uncomplicated cystitis.

Novel nucleotide variations in the thrombomodulin (THBD) gene involved in coagulation pathways can increase the risk of recurrent pregnancy loss (RPL).

Recurrent pregnancy loss (RPL) is a common but complex complication in fertility conditions, affecting about 15-20% of couples. Although several causes have been proposed for RPL, it occurs in about 35-60% of cases without a known explanation. A strong assumption is that genetic factors play a role in the etiology and pathophysiology of PRL. Therefore, several genes are proposed as candidates in the pathogenesis of RPL. The current study aimed to investigate the effects of nucleotide changes in the THBD (thrombomodulin) gene as an RPL-related candidate gene. This gene encodes a cell receptor for thrombin and is involved in reproductive loss in RPL cases. Its involvement in the natural anticoagulant system has been extensively studied. By genetic screening of the entire coding and noncoding regions of the THBD gene, we found twenty-seven heterozygous and homozygous nucleotide changes. Ten of them led to amino acid substitutions, seven variants were identified in the promoter region, and eight of them occurred in 3'UTR. Potentially, the pathogenicity effects of these variations on THBD protein were evaluated by several prediction tools. The numerous genomic variations prompted noticeable modifications of the protein's structural and functional properties. Furthermore, in-silico scores were consistent with deleterious effects for these mutations. The results of this study provide genetic information that will be useful in the future for clinicians, scientists, and students to understand the unknown causes of RPL better. It may also pave the way for developing diagnostic/prognostic approaches to help treat PRL patients.

Prevalence of depressive symptoms and suicidal behaviors among Iranian high school students: A systematic review and meta-analysis.

AIM: The objective of this meta-analysis was to determine the prevalence of depressive symptoms and suicidal behaviors among high-school students in Iran. MATERIALS AND METHODS: A comprehensive search strategy was conducted in the following original databases: PubMed, Web of Science (ISI), Scopus, Psycinfo, and national databases, including the Scientific Information Database (SID) and MagIran, from January 1988 through January 2023. Studies that reported the prevalence of depressive symptoms and suicidal behaviors among high school students in Iran were included. Two investigators extracted all relevant data independently. For deriving mean prevalence rates, random-effects meta-analyses were used. We assessed the quality of studies by the Joanna Briggs Institute (JBI). RESULTS: Total of 67 studies (45,798 participants) were included in the syntheses on depressive symptoms and suicidal ideation. For depressive symptoms, the mean prevalence rate was 48 % (40 %, 55 %). 2804 participants were enrolled for assessing of the prevalence of suicide ideation, and the mean prevalence rate was 21 % (6 %, 36 %). The meta-analysis pooling of the prevalence estimates of suicide attempts was 18 % (15 %, 20 %). CONCLUSIONS: Approximately half of the high school students experience depressive symptoms and, astonishingly, one in five high school students experiences suicidal ideation, so to identify strategies for preventing and treating depressive symptoms and suicidal behaviors in this special population, further research and policymaking are urgently needed.

Grafted Sertoli cells prevent neuronal cell death and memory loss induced by seizures.

Epilepsy significantly reduces the patient's quality of life, and we still need to develop new therapeutic approaches to control it. Transplantation of cells such as Sertoli cells (SCs), having a potent ability to release a variety of growth and immunoprotective substances, have made them a potential candidate to deal with neurological diseases like epilepsy. Hence, this study aims to evaluate whether SCs transplant effectively protects the hippocampus astrocytes and neurons to oppose seizure damage. For this purpose, the effects of bilateral intrahippocampal transplantation of SCs were investigated on the rats with the pentylenetetrazol (PTZ) induced seizure. After one-month, post-graft analysis was performed regarding behavior, immunohistopathology, and the distribution of the hippocampal cells. Our findings showed SCs transplantation reduced astrogliosis, astrocytes process length, the number of branches, and intersections distal to the soma of the hippocampus in the seizure group. In rats with grafted SCs, there was a drop in the hippocampal caspase-3 expression. Moreover, the SCs showed another protective impact, as shown by an improvement in pyramidal neurons' number and spatial distribution. The findings suggested that SCs transplantation can potently modify astrocytes' reactivation and inflammatory responses.

Investigation of the Release Rate of Biocide and Corrosion Resistance of Vinyl-, Acrylic-, and Epoxy-Based Antifouling Paints on Steel in Marine Infrastructures.

This study comprehensively assesses the release rate of biocides, corrosion effects related to antifouling, and the physical properties of different paint types. Tests were conducted to measure thickness, viscosity, hardness, bending, adhesion, gloss, impact resistance, abrasion resistance, scratch resistance, polarization, and salt spray. The paints evaluated include resin-based, acrylic-based, epoxy-based, and vinyl-based formulations. The study investigates the influence of biocide content, biocide particle size, and immersion time on release rate using a lab-scale setup. Results showed that acrylic-based paints had a higher biocide release rate due to faster hydrolysis, while smaller biocide particle sizes led to higher release rates in resin-based paints. Optimal total biocide contents were determined to be 30% for acrylic-based, 60% for epoxy-based, and 50% for vinyl-based paints. Antifouling corrosion analysis demonstrated that sample with an optimal release rate effectively prevent algae growth and fouling. Acrylic-based paint with 30 wt.% biocide content exhibited superior adhesion with a dolly separation force of 4.12 MPa. Evaluating the impact of synthesized polyaniline on 30 wt.% epoxy-based paint, a sample coated with 10 wt.% polyaniline represented a low corrosion rate of 0.35 µm/year and a high impedance value of approximately 37,000 Ohm·cm-2.

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view.

Autophagy is a highly conserved, lysosome-dependent biological mechanism involved in the degradation and recycling of cellular components. There is growing evidence that autophagy is related to male reproductive biology, particularly spermatogenic and endocrinologic processes closely associated with male sexual and reproductive health. In recent decades, problems such as decreasing sperm count, erectile dysfunction, and infertility have worsened. In addition, reproductive health is closely related to overall health and comorbidity in aging men. In this review, we will outline the role of autophagy as a new player in aging male reproductive dysfunction and prostate cancer. We first provide an overview of the mechanisms of autophagy and its role in regulating male reproductive cells. We then focus on the link between autophagy and aging-related diseases. This is followed by a discussion of therapeutic strategies targeting autophagy before we end with limitations of current studies and suggestions for future developments in the field.

Cranial nerve involvement among COVID-19 survivors.

Introduction: COVID-19 was first reported in November 2019 in China and rapidly spread across the globe. COVID-19 causes neurologic symptoms and complications, which may persist even after recovery in patients. The objective of this research was to determine the involvement of cranial nerves in COVID-19 survivors. Method: This was a retrospective study. The study was conducted between March and July of 2022. The analysis included 98 patients with a certain positive polymerase chain reaction. SPSS software version 19 was utilized for data analysis. Results: The average age of the participants was 40.47 years (8.81). The olfactory nerve was found to be the most frequently involved cranial nerve (36.7%). Over 20% of participants had a taste disorder. The findings from the regression analysis indicated that lung involvement and age have a direct and significant relationship with cranial nerve involvement and can serve as its predictors (p = 0.001). Conclusion: It seems that cranial nerve involvement was sustained in COVID-19 patients who survived. In addition, elderly patients and patients with severe illnesses were more likely to show cranial symptoms. It is necessary to monitor COVID-19 survivors for neurological symptoms.

Challenges and solutions in clinical research during the COVID-19 pandemic: A narrative review.

Background and Aims: The COVID-19 pandemic has presented significant challenges to clinical research, necessitating the adoption of innovative and remote methods to conduct studies. This study aimed to investigate these challenges and propose solutions for conducting clinical research during the pandemic. Methods: A narrative review was conducted (approval ID: IR.AMS.REC.1401.029), utilizing keyword searches in PubMed and Web of Science (WOS) citation index expanded (SCI-EXPANDED) from January 2020 to January 2023. Keywords included COVID-19, clinical research, barriers, obstacles, facilitators and enablers. Results: Out of 2508 records retrieved, 43 studies were reviewed, providing valuable insights into the challenges and corresponding solutions for conducting clinical research during the COVID-19 pandemic. The identified challenges were categorized into four main groups: issues related to researchers or investigators, issues related to participants and ethical concerns, administrative issues, and issues related to research implementation. To address these challenges, multiple strategies were proposed, including remote monitoring through phone or video visits, online data collection and interviews to minimize in-person contact, development of virtual platforms for participant interaction and questionnaire completion, consideration of financial incentives, adherence to essential criteria such as inclusion and exclusion parameters, participant compensation, and risk assessment for vulnerable patients. Conclusion: The COVID-19 pandemic has significantly impacted clinical research, requiring the adaptation and enhancement of existing research structures. Although remote methods and electronic equipment have limitations, they hold promise as effective solutions during this challenging period.