Pregnancy outcomes in women with Celiac disease in Northeast Iran: a regional retrospective cohort study.

PURPOSE: To investigate the odds and associations of pregnancy outcomes with exposure to biopsy-confirmed celiac disease (CD) in Northeast Iran. METHODS: In this regional retrospective cohort study, pregnancy records of all women with celiac disease who visited Celiac Disease Clinic of Imam-Reza Hospital from 2017 to 2023 (exposed group) and a sample of women without CD (unexposed group) were extracted using the Electronic Health Record of Mashhad University of Medical Sciences called "Sina". The unexposed group was randomly selected of the database and matched to exposed group on age, location of residence, socioeconomic factors. Our exclusion criteria included age ≥ 45, presence of concomitant disorders, history of non-obstetric uterine surgery, induction of pregnancy through assisted reproductive technology, and any concurrently ongoing pregnancy at the time of study. Pregnancy outcomes evaluated in this study included normal delivery, miscarriage, preterm labor, preeclampsia, and stillbirth. Adjusted odds ratios were calculated using logistic regression adjusted for confounders. RESULTS: Ninety pregnancy records of women with CD and 270 pregnancies of women without CD were included in this study. Low neonatal birthweight (i.e. under 2500 g) had no significant association with CD (aOR = 0.99, 95% CI = 0.92-1.06), as well as postpartum hemorrhage (aOR = 1.12, 95%CI = 0.91-1.38), fetal anomaly (aOR = 0.89, 95%CI = 0.69-1.15), miscarriage (aOR = 1.00, 95%CI = 0.91-1.10), ectopic pregnancy (aOR = 0.94, 95%CI = 0.73-1.20), preterm labor (aOR = 1.00, 95%CI = 0.92-1.10), gestational diabetes mellitus (aOR = 1.07, 95%CI = 0.98-1.16), gestational hypertension (aOR = 0.99, 95%CI = 0.89-1.11), and gestation hypothyroidism (aOR = 0.95, 95%CI = 0.82-1.11). However, we found significantly lower odds of preeclampsia in pregnancies affected by CD (aOR = 0.83, 95%CI = 0.69-0.99). CONCLUSION: Celiac disease was not associated with increased odds of low neonatal birthweight, postpartum hemorrhage, fetal anomaly, miscarriage, ectopic pregnancy, preterm labor, gestational diabetes mellitus, gestational hypertension and gestational hypothyroidism. Preeclampsia had significantly lower odds in pregnancies affected with CD.

The distribution of neurotransmitters in the brain circuitry: Mesolimbic pathway and addiction.

Understanding the central nervous system (CNS) circuitry and its different neurotransmitters that underlie reward is essential to improve treatment for many common health issues, such as addiction. Here, we concentrate on understanding how the mesolimbic circuitry and neurotransmitters are organized and function, and how drug exposure affects synaptic and structural changes in this circuitry. While the role of some reward circuits, like the cerebral dopamine (DA)/glutamate (Glu)/gamma aminobutyric acid (GABA)ergic pathways, in drug reward, is well known, new research using molecular-based methods has shown functional alterations throughout the reward circuitry that contribute to various aspects of addiction, including craving and relapse. A new understanding of the fundamental connections between brain regions as well as the molecular alterations within these particular microcircuits, such as neurotrophic factor and molecular signaling or distinct receptor function, that underlie synaptic and structural plasticity evoked by drugs of abuse has been made possible by the ability to observe and manipulate neuronal activity within specific cell types and circuits. It is exciting that these discoveries from preclinical animal research are now being applied in the clinic, where therapies for human drug dependence, such as deep brain stimulation and transcranial magnetic stimulation, are being tested. Therefore, this chapter seeks to summarize the current understanding of the important brain regions (especially, mesolimbic circuitry) and neurotransmitters implicated in drug-related behaviors and the molecular mechanisms that contribute to altered connectivity between these areas, with the postulation that increased knowledge of the plasticity within the drug reward circuit will lead to new and improved treatments for addiction.

Factors influencing mortality in COVID-19-associated mucormycosis: The international ID-IRI study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first 3 months post-COVID-19 diagnosis. Data collected through the ID-IRI included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29 ± 13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis. Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age (hazard ratio [HR] = 1.06, [P < .001]), rituximab use (HR = 21.2, P = .05), and diabetic ketoacidosis (HR = 3.58, P = .009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR = 8.81, P < .001). The utilization of rituximab and diabetic ketoacidosis, along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments, and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

Dental stem cells improve memory and reduce cell death in rat seizure model.

Epilepsy is a common neurological disorder that significantly affects the quality of life of patients. In this study, we aim to evaluate the effectiveness of dental pulp stem cell (DPSC) transplantation in decreasing inflammation and cell death in brain cells, thus reducing seizure damage. We induced seizures in rats using intraperitoneal injections of pentylenetetrazole (PTZ). In the PTZ + DPSC group, we conducted bilateral hippocampal transplantation of DPSCs in PTZ-lesioned rat models. After 1 month, we performed post-graft analysis and measured some behavioral factors, such as working memory and long-term memory, using a T-maze test and passive avoidance test, respectively. We investigated the immunohistopathology and distribution of astrocyte cells through light microscopy and Sholl analysis. Additionally, we employed the Voronoi tessellation method to estimate the spatial distribution of the cells in the hippocampus. Compared to the control group, we observed a reduction in astrogliosis, astrocyte process length, the number of branches, and intersections distal to the soma in the hippocampus of the PTZ + DPSC group. Further analysis indicated that the grafted DPSCs decreased the expression of caspase-3 in the hippocampus of rats with induced seizures. Moreover, the DPSCs transplant protected hippocampal pyramidal neurons against PTZ toxicity and improved the spatial distribution of the hippocampal neurons. Our findings suggest that DPSCs transplant can be an effective modifier of astrocyte reactivation and inflammatory responses.

Prevalence of linezolid resistance in Streptococcus pneumoniae isolates: a systematic review and meta-analysis.

Aim: This study aimed to understand the current level of linezolid (LNZ) resistance in Streptococcus pneumoniae isolates reported over the past 10 years. Material & methods: An electronic search was conducted for the following keywords: ((Streptococcus pneumoniae [title/abstract]) OR (Pneumococcus [title/abstract]) OR (Pneumococci [title/abstract]) AND (linezolid [title/abstract]) OR (Zyvox [title/abstract])) OR (Zyvoxid [title/abstract])). Result: Out of all the studies, 80 had a cross-sectional design, while 11 followed a cohort approach. The prevalence of LNZ resistance among S. pneumoniae isolates ranged from 0% to 4.86%. Discussion: Urgent, high-powered, randomized, controlled trials with participants from endemic regions are needed to gain a comprehensive understanding of the impact on and significance of LNZ treatment to patients.

Effects of ultra-filtration purification of infectious bursal disease virus on immune responses and cytokine activation in specific pathogen free chickens.

Purification is an important step in the production of viral vaccines that strongly affects product recovery and subsequent immune responses. The present study was carried out with the aim of improving the purification of infectious bursal disease virus (IBDV) by the tangential flow filtration (TFF) method. Then, the effect of the purified virus on the induction of immune responses against IBDV in specific pathogen free (SPF) chickens was investigated. The IBD07IR strain was propagated in embryonated SPF eggs. The virus was purified using a 100 kDa cassette. The quality of the recovered viruses was evaluated by titration. A total number of 60 SPF chickens were randomly divided into three groups (n = 20) and received the concentrated viral antigen, commercial live IBDV vaccine and phosphate-buffered saline at the age of 3 weeks by eye drop method. The bursa of Fabricius was examined histopathologically for possible changes. Sera were collected at 1-week intervals from day 0 until the end of 6 weeks after vaccination. The IBDV-specific antibody levels, induction of cell-mediated immunity and mRNA expression levels of cytokines were evaluated. The results showed that despite a relative raise in virus titer from 7.66 to 8.17 embryo infectious dose (EID)50 mL-1 following purification, both the purified IBDV and commercial vaccine are able to induce strong immune responses against the virus. Within a context of egg-based IBDV vaccine production, a single-step TFF can be applied for the relatively purification. This platform requires a further study in the selection of multiple membranes to optimize the operating conditions and final product.

Transmission of behavioral and cognitive impairments across generations in rats subjected to prenatal valproic acid exposure.

BACKGROUND: Autism spectrum disorder (ASD) represents an inheritable neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Numerous studies have underscored the significant roles played by genetic and environmental factors in the etiology of ASD, and these factors are known to perpetuate behavioral impairments across generations. OBJECTIVES: The primary objective of this study was to assess the behavioral and cognitive attributes in the second filial (F2) generation of male and female rats, with a particular focus on those whose parents had been exposed to valproic acid (VPA) during embryonic development. METHODS: In this study, a cohort of 32 male and 32 female rats from the second filial (F2) generation, referred to as Mother.ASD, Father.ASD, or Both.ASD, was examined. These designations indicate whether the mother, father, or both parents had experienced embryonic exposure to valproic acid (600 mg/kg, i.p.). During adolescence, the F2 pups underwent behavioral and cognitive assessments, including open field testing, marble burying, social interaction evaluations, and Morris water maze tasks. RESULTS: Our data revealed that while both the Mother.ASD and Father.ASD groups, regardless of sex, exhibited elevated anxiety-like behavior in the open field test. Only the Mother.ASD group displayed repetitive behaviors and deficits in social memory. Additionally, spatial memory impairments were observed in both sexes. These findings highlight the transmission of autistic-like behaviors in the offspring of Mother.ASD rats from both sexes. Nevertheless, future research endeavors should be more targeted in identifying the specific genes responsible for this transmission. CONCLUSION: In summary, our findings underscore the transmission of autistic-like behaviors, including anxiety-like behavior, repetitive actions, impairments in social interactions, and deficits in memory, to the offspring of the Mother.ASD group, irrespective of their sex.

Mucormycosis, New Causative Agents, and New Susceptible Populations: Review of Cases in a Tertiary Care Hospital in Iran (2007-2021).

Background: Mucormycosis is an aggressive opportunistic fungal infection that afflicts patients with severe underlying immunosuppression, uncontrolled hyperglycemia and/or ketoacidosis, iron overload, and occasionally healthy patients who are inoculated with fungal spores through traumatic injuries. The epidemiology of mucormycosis has changed after the COVID-19 pandemic, with mucormycosis becoming the most common and the fatal coinfection. Methods: In a retrospective, cross-sectional study, 82 hospitalized patients with a definite diagnosis of mucormycosis were reported from 2007 to 2021 in a referral, tertiary care center in Tehran, Iran. Results: The number of post-COVID cases increased 4.6 times per year, with 41.5% of patients admitted during the two years of the pandemic. Mucormycosis was more common in women (57.3%), and the most common underlying diseases were diabetes (43.7%), both COVID-19 and diabetes (23.2%), cancer (11%), rheumatic diseases (7.3%), COVID-19 without other underlying diseases (6.1%), and transplantation (4.9%). Rhino-orbito-cerebral Mucormycosis (54.9%) followed by Sino-orbital infection (23.2%) was the most common presentation. There was a significant relationship between the use of immunosuppressive agents and the development of Mucormycosis (P<0.005) The average mortality was 41.5%, but this ratio decreased to 35% during the pandemic era. Conclusion: The COVID-19 pandemic caused a 4.6-fold increase in the number of mucormycosis patients, and there was a significant relationship between hyperglycemia, corticosteroid use, and mucormycosis. The death rate during the COVID-19 pandemic has decreased by 6.5%, and during the COVID period, the interval between the arrival of a patient with mucormycosis and the start of the correct treatment was significantly decreased.

Lupus Anticoagulant Is Associated with Critical Cases and High Mortality in COVID-19: A Literature Review.

Background: In severe COVID-19 cases, a hypercoagulable state may occur. Antiphospholipid syndrome-related auto-antibodies (APSRAs) contribute to coagulopathy, but their role in COVID- 19 remains unclear. We aimed to investigate the prevalence of positive APSRAs and their effect on clinical outcomes in confirmed COVID-19 patients. Materials and Methods: In this cross-sectional study, severe hospitalized COVID-19 cases were enrolled. Demographic and clinical data were obtained from the day of admission. APSRAs including IgG and/or IgM anticardiolipin (aCL) and anti-ß2-glycoprotein1 (anti-ß2GP1) as well as lupus anticoagulant (LAC) were measured. Results: In this study, 54 severe COVID-19 cases with positive RT-PCR and chest CT scans were recruited. Positive APSRAs were found in 7 (12.9%) patients. Positive LAC was a more prevalent marker as compared to other tests (11.1%). The prevalence of positive aCL (IgM or IgG) and anti-ß2 GPI (IgM or IgG) was 1.8% (in an elderly woman). Lower oxygen saturation was found in the positive APSRAs group as opposed to the negative APSRAs group (70.3±9 vs. 84.8±9.7%). The mortality rate in the positive APSRAs group was significantly higher relative to the negative APSRAs group (83.3% vs. 27.1%; P-value: 0.01). Likewise, the mechanical ventilation requirement in the positive group was also higher (50% vs. 27.1%, P-value: 0.28). Conclusion: This study indicated that LAC might be associated with critical cases and high mortality of COVID-19. Nonetheless, the mortality was not related to macrothrombotic incidence.

Down-regulating CD19 surface markers expression correlates with infectious bursal disease virus replication.

The infectious bursal disease virus (IBDV) causes an acute and highly contagious immunosuppressive response in young chickens by targeting B lymphocytes in immune organs. Changes in regulatory T-cell ratio and apoptosis have been demonstrated during IBDV infection in these cells. The possible change in CD19 expression as the precursor of B cells after IBDV replication was detected in this study. Raji cells were infected with an IBDV isolate at MOIs of 1.0 and 3.0. The viral kinetics were determined using the characteristic virus-induced CPE, cell viability, and infectious titer. Induction of apoptosis and also changes in the CD19 expression within the virus infection were assessed by flow cytometry. The Raji cells were found to be susceptible to IBDV infection by producing marked CPEs dependent on MOI. The infectivity titers were determined in intra- and extracellular samples at the defined hours. The kinetics of early IBDV replication in Raji cells were nearly identical for both MOIs, but a significant difference in the infectivity titer was observed at 48 hpi. The quick apoptotic events were observed to be significantly higher in MOI 3.0, which was correlated with the lower virus titer. A significant CD19 expression change in the IBDV-infected Raji cells was revealed. The results suggested that Raji cells mimic the IBDV replication in lymphoid organs and the virus replication is related to CD19 expression frequencies in the lymphoid cells.

The human neuroprotective placental protein composition suppressing tinnitus and restoring auditory brainstem response in a rodent model of sodium salicylate-induced ototoxicity.

The effect of neuroprotective placental protein composition (NPPC) on the suppression of tinnitus and the restoration of the auditory brainstem response (ABR) characteristics was explored in tinnitus-induced rats. The animals were placed into two groups: (1) the study group, rats received sodium salicylate (SS) at the dose of 200 mg/kg twice a day for two weeks, and then 0.4 mg of the NPPC per day, between the 14th and 28th days, (2) the placebo group, rats received saline for two weeks, and then the NPPC alone between the 14th and 28th days. The gap pre-pulse inhibition of the acoustic startle (GPIAS), the pre-pulse inhibition (PPI), and the ABR assessments were performed on animals in both groups three times (baseline, day 14, and 28). The GPIAS value declined after 14 consecutive days of the SS injection, while NPPC treatment augmented the GPIAS score in the study group on the 28th day. The PPI outcomes revealed no significant changes, indicating hearing preservation after the SS and NPPC administrations. Moreover, some changes in ABR characteristics were observed following SS injection, including (1) higher ABR thresholds, (2) lowered waves I and II amplitudes at the frequencies of 6, 12, and 24 kHz and wave III at the 12 kHz, (3) elevated amplitude ratios, and (4) prolongation in brainstem transmission time (BTT). All the mentioned variables returned to their normal values after applying the NPPC. The NPPC use could exert positive therapeutic effects on the tinnitus-induced rats and improve their ABR parameters.

Different Approaches for the Preparation of Composite Ionic Liquid-Based Membranes for Proton Exchange Membrane Fuel Cell Applications-Recent Advancements.

The use of ionic liquid-based membranes as polymer electrolyte membranes for fuel cell applications increases significantly due to the major features of ionic liquids (i.e., high thermal stability and ion conductivity, non-volatility, and non-flammability). In general, there are three major methods to introduce ionic liquids into the polymer membrane, such as incorporating ionic liquid into a polymer solution, impregnating the polymer with ionic liquid, and cross-linking. The incorporation of ionic liquids into a polymer solution is the most common method, owing to easy operation of process and quick membrane formation. However, the prepared composite membranes suffer from a reduction in mechanical stability and ionic liquid leakage. While mechanical stability may be enhanced by the membrane's impregnation with ionic liquid, ionic liquid leaching is still the main drawback of this method. The presence of covalent bonds between ionic liquids and polymer chains during the cross-linking reaction can decrease the ionic liquid release. Cross-linked membranes reveal more stable proton conductivity, although a decrease in ionic mobility can be noticed. In the present work, the main approaches for ionic liquid introduction into the polymer film are presented in detail, and the recently obtained results (2019-2023) are discussed in correlation with the composite membrane structure. In addition, some promising new methods (i.e., layer-by-layer self-assembly, vacuum-assisted flocculation, spin coating, and freeze drying) are described.

Music alleviates cognitive impairments in an animal model of autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms including impairment in social communication and restrictive and repetitive behaviors and interests. Music has emerged in the past decade as an intervention therapy for children with ASD. The aim of the present study was to evaluate the effects of music on cognition impairments in the valproic acid (VPA) rat model of autism. The VPA was administered for animal modeling of autism on embryonic day 12.5 (E12.5) (600 mg/kg). Male and female pups were sub divided into four main groups (Saline.Non-music, VPA.Non-music, Saline.Music, and VPA.Music). The rats in the music groups were exposed to Mozart's piano sonata K.448 for 30 days (4 h/day), from postnatal day (PND) 21 to 50. Autistic-like behaviors were tested using a social interaction, the Morris water maze (MWM), and a passive avoidance tasks at the end of the PND 50. Our results demonstrated that VPA-exposed rat pups had significantly lower sociability and social memory performance compared with the saline-exposed rats in both sexes. VPA-exposed rat pups exhibited learning and memory impairments in the MWM and passive avoidance tasks. Our results demonstrated that music improved sociability in VPA-exposed rats, especially in males. Furthermore, our findings revealed that music improved learning impairments in VPA-exposed male rats in MWM task. In addition, music improved spatial memory impairments in VPA-exposed rats of both sexes. We also found that music improved passive avoidance memory impairments in VPA-exposed rats of both sexes, especially in females. More investigation in future studies are needed.

Investigation of the biofilm formation in extra-intestinal pathogenic Escherichia coli ST131 strains and its correlation with the presence of fimH, afa, and kpsMSTII genes.

Escherichia coli sequence type 131 (ST131) is a multidrug-resistant strain with the global dissemination. Biofilm formation-related factors include the most important virulence factors in extra-intestinal pathogenic E. coli (ExPEC) ST131 strains causing infections with treatment-limited subjects. This study aims to investigate the biofilm formation ability and its correlation with the presence of fimH, afa, and kpsMSTII genes in clinical isolates of ExPEC ST131. In this regard, the prevalence and characteristics of these strains collected and evaluated. The results revealed strong, moderate, and weak attachment abilities related to biofilm formation attributes in 45%, 20%, and 35% of strains, respectively. In the meantime, the frequency of the fimH, afa, and kpsMSTII genes among the isolates was observed as follows: fimH positive: 65%; afa positive: 55%; and kpsMSTII positive: 85%. The results convey a significant different of biofilm formation ability between clinical E. coli ST131 and non-ST131 isolates. Furthermore, while 45% of ST131 isolates produced strong biofilms, only 2% of non-ST131 isolates showed the ability to form strong biofilms. The attending of fimH, afa, and kpsMSTII genes in the majority of ST131 strains demonstrated a key role leading to biofilm formation. These findings suggested the application of fimH, afa, and kpsMSTII gene suppressors for treating biofilm infections caused by drug-resistant ST131 strains.

Prevalence of hypertension and its associated factors among professional drivers: a population-based study.

OBJECTIVE: Hypertension is one of the most important causes of cardiovascular disease. It has been found that professional drivers are at high risk of hypertension. This study has been performed to determine the prevalence of hypertension and its associated factors among professional drivers in Shahroud. METHODS AND RESULTS: In this study, the prevalence of hypertension was determined according to the definition by the American Heart Association among 1461 professional drivers participating in the first cross-sectional phase of Shahroud drivers' prospective cohort study. The prevalence of elevated blood pressure and hypertension was examined based on the initial age, and gender presented, along with the factors affecting this disease based on multinomial logistic regression. The prevalence of elevated blood pressure, stage 1 and 2 hypertension was 46.9%, 6%, and 1.3%, respectively. In the multivariate multinomial logistic regression model, having diabetes, Body Mass Index ≥25, and driving years was associated with an increased chance of developing elevated blood pressure and hypertension. CONCLUSIONS: Attention should be paid to high prevalence of elevated blood pressure and hypertension among professional drivers in Iran as a health priority for drivers. Plans should be made to reduce it as well as to prevent its complications.

Comparative Transcriptome Analysis Unveils the Molecular Mechanism Underlying Sepal Colour Changes under Acidic pH Substratum in Hydrangea macrophylla

The hydrangea (Hydrangea macrophylla (Thunb). Ser.), an ornamental plant, has good marketing potential and is known for its capacity to change the colour of its inflorescence depending on the pH of the cultivation media. The molecular mechanisms causing these changes are still uncertain. In the present study, transcriptome and targeted metabolic profiling were used to identify molecular changes in the RNAome of hydrangea plants cultured at two different pH levels. De novo assembly yielded 186,477 unigenes. Transcriptomic datasets provided a comprehensive and systemic overview of the dynamic networks of the gene expression underlying flower colour formation in hydrangeas. Weighted analyses of gene co-expression network identified candidate genes and hub genes from the modules linked closely to the hyper accumulation of Al3+ during different stages of flower development. F3'5'H, ANS, FLS, CHS, UA3GT, CHI, DFR, and F3H were enhanced significantly in the modules. In addition, MYB, bHLH, PAL6, PAL9, and WD40 were identified as hub genes. Thus, a hypothesis elucidating the colour change in the flowers of Al3+-treated plants was established. This study identified many potential key regulators of flower pigmentation, providing novel insights into the molecular networks in hydrangea flowers.

Stability improvement of polyaniline nanocomposite immunosensor for early detection of insulin receptor antibody as biomarker of type 2 diabetes.

Polyaniline nanocomposite with controllable properties was used to design and fabricate a novel electrochemical immunosensor for the early detection of type 2 diabetes. Insulin receptor antibody is a powerful predictor of type 2 diabetes development in individuals. A systematic study was carried out to investigate the effects of different polyaniline layers and the Nafion layer on the morphological, chemical, and electrochemical properties of nanocomposite immunosensor, especially the stability. The bioengineered Nafion-Au nanoparticles-polyaniline/gold electrode demonstrated outstanding electrocatalytic performance in the detection of insulin receptor antibodies with a high sensitivity (136.21 µA.ng-1.ml.cm-2) in a linear range from 0.001 to 200 ng.ml-1 as well as a low detection limit of 1.827 pg.ml-1, response time within 10 min, remarkable selectivity, and significant stability of 80 days. Therefore, the developed immunosensor is a suitable nanocomposite platform for insulin receptor antibody level determination in human plasma.

Sida rhombifolia Exerts Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer HepG2 Cells in Vitro.

PURPOSE: Modern research revealed that plants belonging to the Sida rhombifolia family (Malvaceae) contain biologically active compounds that make them prone to discovering and developing anticancer drugs. This study aimed to evaluate the apoptosis effects of S. rhombifolia extracts in HepG2 Cell Line was performed. METHODS: The extractions were prepared, and an MTT assay was applied to evaluate its role in decreasing the viability of HepG2 and HFF cells. Phenolic compounds were analyzed using High-performance liquid chromatography (HPLC). FlowCytometry and RT-qPCR evaluated apoptosis was performed to measure the mRNA expression of pro-and anti-apoptotic mediators. RESULTS: The results can be summarized as EtOAc extract was more cytotoxic against the HepG2 cells (IC50= 364.3 µg/mL) compared to MeOH and HEX extracts (720.2 µg/mL) (560.4 µg/mL) with less cytotoxicity in HFF cells (353.2 µg/mL). The HPLC analysis results revealed most phenolic compounds, such as Epicatechin(1.3 mg/g). The EtOAc extract (300 µg/mL) induced 34% apoptosis in HepG2 cells. RT-qPCR data showed upregulation of the proapoptotic gene (Bax) and increased Bax/BCL-2 ratio by S. rhombifolia EtOAc extract (300 µg/mL). CONCLUSION: In conclusion, the EtOAc extract of S. rhombifolia is capable of inducing apoptosis in HepG2 cells through modulation of the mitochondrial pathway, which explains their antitumor activity.

A2A adenosine receptor agonist reduced MMP8 expression in healthy M2-like macrophages but not in macrophages from ankylosing spondylitis patients.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease that mostly affects different joints of the body. Macrophages are the predominant cells that mediate disease progression by secreting several pro-inflammatory mediators. Different receptors are involved in macrophages' function including the adenosine receptors (AR). Our main objective in this study was to assess the effect of applying A2A adenosine receptor agonist (CGS-21,680) on the gene expression of inflammatory mediators including bone morphogenetic proteins (BMP)-2, 4 and matrix metalloproteinases (MMP)-3, 8, 9, and 13 on the macrophages from AS patients compared to healthy macrophages. METHODS: Monocytes were isolated from the whole blood of 28 individuals (AS patients and healthy controls in a 1:1 ratio). Macrophages were differentiated using macrophage colony-stimulating factor (M-CSF), and flow cytometry was performed to confirm surface markers. CGS-21,680 was used to treat cells that had been differentiated. Using SYBR green real-time PCR, relative gene expression was determined. RESULTS: Activating A2AAR diminished MMP8 expression in healthy macrophages while it cannot reduce MMP8 expression in patients' macrophages. The effect of A2AAR activation on the expression of BMP2 and MMP9 reached statistical significance neither in healthy macrophages nor in the patients' group. We also discovered a significant positive connection between MMP8 expression and patient scores on the Bath ankylosing spondylitis functional index (BASFI). CONCLUSION: Due to the disability of A2AAR activation in the reduction of MMP8 expression in patients' macrophages and the correlation of MMP8 expression with BASFI index in patients, these results represent defects and dysregulations in the related signaling pathway in patients' macrophages.

The effect of dopaminergic neuron transplantation and melatonin co-administration on oxidative stress-induced cell death in Parkinson's disease.

A gradual degeneration of the striatum and loss of nigral dopamine cells are characteristic of Parkinson's disease. Nowadays, combination therapy for neurodegenerative disease is considered. This study aimed to investigate the effects of melatonin and dopaminergic neurons derived from adipose tissue stem cells (ADSCs) in a rat model of Parkinson's disease. Parkinson's disease was induced in rats using neurotoxin 6-Hydroxydopamine. The treatment was performed using melatonin and dopaminergic neurons transplantation. Subsequently, behavioral tests, western blot analysis for Caspase-3 expression, GSH (Glutathione) content and stereology analysis for the volume and cell number of substantia nigra and striatum were performed. Treatment with melatonin and dopaminergic neuron transplantation increased the number of neurons in substantia nigra and striatum while the number of glial cell and the volume of substantia nigra and striatum did not show significant change between groups. Western blot analysis for caspase 3 indicated the significant differences between groups. The results also indicated the increased level of glutathione (GSH) content in treatment groups. this study showed that combination therapy with melatonin and dopaminergic neurons could greatly protect the neurons, reduce oxidative stress and improve the symptoms of PD.