Sex-dependent alterations of inflammatory factors, oxidative stress, and histopathology of the brain-gut axis in a VPA-induced autistic-like model of rats.

INTRODUCTION: In this study, we aimed to investigate the inflammatory factors, oxidative stress, and histopathological consequences of the brain-gut axis in male and female rats prenatally exposed to VPA. METHODS: Pregnant Wistar rats were randomly divided into two groups. The animals received saline, and valproic acid (VPA) (600 mg/kg, i.p.) on embryonic day 12.5 (E12.5). All offspring were weaned on postnatal day 21, and the experiments were done in male and female rats on day 60. The brain and intestine tissues were extracted to assess histopathology, inflammation, and oxidative stress. RESULTS: An increase of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and a decrease of interleukin-10 (IL-10) were observed in the two sexes and two tissues of the autistic rats. In the VPA-exposed animals, malondialdehyde (MDA) and protein carbonyl (PC) increased in the brain of both sexes and the intestines of only the males. The total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased in both tissues of male and female autistic groups. Histopathological evaluation showed that the %apoptosis of the cortex in the autistic male and female groups was more than in controls whereas this parameter in the CA1 and CA3 was significant only in the male rats. In the intestine, histopathologic changes were seen only in the male autistic animals. CONCLUSION: The inflammatory and antioxidant factors were in line in the brain-gut axis in male and female rats prenatally exposed to VPA. Histopathological consequences were more significant in the VPA-exposed male animals.

Long non-coding RNAs as potential biomarkers or therapeutic targets in gastric cancer.

Aim: This study aimed to find lncRNAs and mRNAs that were expressed differently by combining microarray datasets from different studies. This was done to find important target genes in gastric cancer for anti-cancer therapy. Background: Gastric cancer (GC) is the fourth most frequent and second-most deadly malignancy worldwide. Thus, genetic diagnosis and treatment should focus on genetic and epigenetic variables. Based on several studies, disordered expression of non-coding RNAs (ncRNAs), such as lncRNAs, regulate gastric cancer invasion and metastasis. Besides, lncRNAs cooperatively regulate gene expression and GC progression. Methods: We obtained differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) from three GC tissue microarray datasets by meta-analysis and screened genes using the "Limma" package. Then, using the RNAInter database, we allocated DEmRNAs to each DElncRNA. ClusterProfiler and GOplot programs were used to analyze function enrichment pathways and gene ontologies for final DEmRNAs. Results: A total of 9 differentially expressed lncRNAs (DElncRNAs) (5 up-regulated and 4 down-regulated), and 856 DEmRNAs (451 up-regulated and 405 down-regulated) between tumor and adjacent normal samples were found. Finally, 117 differentially expressed mRNAs were predicted as interactors of six DElncRNAs (H19, WT1-AS, EMX2OS, HOTAIR, ZEB1-AS1, and LINC00261). Conclusion: In order to promote cancer therapeutics and give knowledge on the process of carcinogenesis, our study projected a network of drug-gene interactions for discovered genes and presented relevant prospective biomarkers for the prognosis of patients with stomach cancer.

Assessment of the Effect of Sub-Cutaneous Adalimumab on Prognosis of COVID-19 Patients: a Non-Randomized Pilot Clinical Trial Study in Iran.

BACKGROUND: Adalimumab is an anti-inflammatory medicine used to treat a variety of disorders, although its effectiveness in improving the clinical status of COVID-19 patients is debatable. The goal was to evaluate the efficacy of adalimumab as an alternate treatment in COVID-19 patients. METHODS: This non-randomized pilot clinical trial study included 18 patients with severe COVID-19 status hospitalized at the Afzalipour Hospital in Kerman from February 2022 to March 2022. Patients were divided into two groups: nine patients in the control group received dexamethasone, remdesivir, and heparin in addition to supportive therapies. The case group also included nine patients who received adalimumab injection (CinnoRA®, CinnaGen, Iran) in addition to the treatment administered to the control group. RESULTS: Although the effect of adalimumab injection on clinical factors, including mechanical ventilation required, the number of days oxygen needed, the length of stay in the intensive care unit (ICU), and saturation of peripheral oxygen (SpO2) level and respiratory rate (RR), were not significantly different between groups, the intra-group SpO2 level before and after receiving oxygen was significantly different in the case group (p ≤ 0.001 and p = 0.002). In addition, laboratory tests for lactate dehydrogenase (LDH) and C-reactive protein (CRP) revealed no statistically significant differences between the two groups. Nonetheless, a positive intra-group effect of the medication was detected on these two parameters. No short-term side effects of drug injection were observed. CONCLUSIONS: This study demonstrated the efficacy of adalimumab as an alternate medication for improving SpO2, LDH, and CRP levels in COVID-19 patients.

Higher Risk of Chronic Hepatitis E Virus Infection in Patients with Human Immunodeficiency Virus-1: An Iranian Cross-sectional Study.

Background & Objective: Occurrence of Hepatitis E Virus (HEV) infection may be common in Human Immunodeficiency Virus (HIV-1) patients and may lead to chronic infection as well as cirrhosis. We intended to determine the incidence of HEV infection among HIV-1 patients compared to individuals without HIV-1 infection. Methods: In our cross-sectional study, 87 HIV-1-positive patients were compared to 93 healthy individuals in Kerman, Iran. Plasma and peripheral blood mononuclear cells (PBMCs) were obtained from all the participants. Plasma samples were evaluated for HEV IgM and IgG using the ELISA kit. Then, reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) was used in RNA extractions from PBMCs to check for the presence of HEV RNA. Results: Among the subjects examined in our study, 61 (70.1%) and 71 (77.4%) out of patients with HIV-1 infection and healthy individuals were male, respectively. The average ages of patients with HIV-1 and the control group were 40.2 years and 39.9 years, respectively. No discernible differences were found between the two groups based on IgM and IgG seropositivity against the HEV. However, HEV-RNA was found in 8% of patients with HIV-1 and 1.1% of HIV-1-negative individuals (P=0.03). There was also an association between the HEV genome and anti-HEV and anti-HCV antibodies in HIV-1-positive patients (P=0.02 and P=0.014, respectively). Conclusion: HEV infection may be more common in HIV-1 patients and may develop a chronic infection in immunocompromised individuals. Molecular-based HEV diagnostic tests, including RT-PCR assays, should be performed in HIV-1 patients with unknown impaired liver function tests.

Mediterranean spotted fever as a non-endemic disease in the southeast of Iran: Diagnosis and treatment based on specific skin lesion.

Key Clinical Message: Rickettsia spp. should be investigated if Tache Noire, as a dark plaque covering a superficial ulcer surrounded by scale, edema, and erythema, are observed, even in non-endemic areas of Rickettsia spp. Abstract: A 31-year-old man with fever, dyspnea, abdominal pain, and jaundice has been admitted to the hospital in the southeast of Iran. Due to the presence of a pathognomonic skin lesion (Tache noire), the patient was diagnosed with Mediterranean spotted fever (MSF) and was treated with doxycycline, without waiting for PCR and IFA findings.

HAV-induced acalculous cholecystitis: A case report and literature review.

Hepatitis A virus (HAV) has some life-threatening extrahepatic complications, such as acute acalculous cholecystitis (AAC). We present HAV-induced AAC in a young female, based on clinical, laboratory, and imaging findings, and conduct a literature review. The patient became irritable, which progressed to lethargy, as well as a significant decline in liver function, indicating acute liver failure (ALF). She was immediately managed in the intensive care unit with close airway and hemodynamic monitoring after being diagnosed with ALF (ICU). The patient's condition was improving, despite only close monitoring and supportive treatment with ursodeoxycholic acid (UDCA) and N-acetyl cysteine (NAC).

Mortality Trends of Gastrointestinal, Liver, and Pancreaticobiliary Diseases: A Hospital-Based Prospective Study in the Southeast of Iran.

Background: Gastrointestinal (GI), liver, and pancreaticobiliary diseases, in addition to the high health care utilization, account for a significant proportion of disability and death in Iran. We aimed to assess the incidence of in-hospital mortality for the total GI, liver, and pancreaticobiliary diseases in all hospitals in Kerman, Iran. Methods: In a cross-sectional study from May 2017 to April 2018, we collected the data of in-hospital death records due to GI, liver, and pancreaticobiliary diseases in all hospitals in Kerman city. GI and liver diseases were classified into three main categories: 1. Non-malignant GI diseases, 2. Non-malignant liver and pancreaticobiliary diseases, and 3. GI, liver, and pancreaticobiliary malignancies. All data were analyzed using SPSS software, version 22 (IBM). Results: Of 3427 in-hospital mortality, 269 (7.84%) deaths were due to GI, liver, and pancreaticobiliary diseases, of which 82 (30.48%) were related to non-malignant GI disorders, 92 (34.20%) to the non-malignant liver and pancreaticobiliary diseases, and 95 (35.31%) were associated with GI, liver and pancreaticobiliary malignancies. Most patients were male (62.08%), and the most common age was between 60-80 years (40.5%). GI bleeding occurred in 158 (58.73%) patients, and variceal bleeding was the most common cause (28.48%). Additionally, cirrhosis was reported in 41 out of 92 (44.56%), and hepatitis B virus (HBV) was the most common cause of cirrhosis among 17 out of 41 (41.46%). Conclusion: Our results show that gastric, colorectal, and pancreatic cancers and cirrhosis due to HBV were the most common causes of mortality associated with GI, liver, and pancreaticobiliary diseases in the hospitals of Kerman.

The Association between Oral Hygiene and Gastric Pathology in Patients with Dyspepsia: a Cross-Sectional Study in Southeast Iran.

BACKGROUND Many studies have reported an association between periodontal infections and some systemic diseases such as respiratory and cardiovascular diseases. Some studies found a direct association between chronic gastritis caused by Helicobacter pylori (HP) infection and poor periodontal health. METHODS In a cross-sectional study from November 2014 to December 2015 in Kerman, the largest province in southeast Iran, patients with dyspepsia who were candidate for diagnostic upper gastrointestinal (GI) endoscopy were included in our study. Decayed, Missing, and Filled Teeth (DMFT) index and Loe plaque index that are two popular indexes in dental epidemiology were used to assess the oral health by a dentist before the upper GI endoscopy. According to the Loe plaque index, score: 0= no plaque, score: 1= a film of plaque attaching to the free gingival border and near area of the tooth, score: 2= moderate reposition of deposits within the gingival pocket, score :3= plenty of soft matter within the gingival pocket±on the tooth and gingival border. Scores ≤1, 2 and 3 equal to good, moderate, and poor oral hygiene, respectively. During upper GI endoscopy a total of six biopsy samples were taken from fundus, body, and antrum. A pathologist reported these samples according to Sidney's classification into superficial gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia. RESULTS According to Sidney's classification 77 (89.5%) patients had superficial gastritis, 3 (3.5%) had atrophic gastritis, and 6 (7%) had intestinal metaplasia. HP was found in 80.2% of the gastric mucosal biopsy samples. There were not statistically significant relationship between Sidney's classification, presence of HP in gastric mucosal biopsies, and hygiene indicators (p>0.05). No relation was found between the DMFT index and superficial gastritis, atrophic gastritis, and intestinal metaplasia (p>0.05). Gastric infection with HP was found in 70%, 75%, and 100% of patients with mild, moderate, and sever DMFT index, respectively. CONCLUSION Our study showed that there might be a relation between poor oral hygiene and gastric precancerous lesions. In addition, HP infection in gastric histopathology might be associated with periodontal disease.

Small bowel bacterial overgrowth in patients with irritable bowel syndrome: the first study in iran.

BACKGROUND Small intestinal bacterial overgrowth (SIBO) may have a role in the pathophysiology of irritable bowel syndrome (IBS). So, the aim of this study was to assess the association between SIBO and IBS by using glucose breath test (GBT) in Kerman city as the first study in Iranian population. METHODS 107 patients with IBS and 107 healthy individuals were enrolled in our study. All the participants underwent GBT. A peak of H2 values >20 p.p.m above the basal value after glucose ingestion was considered suggestive of SIBO. SPSS software version 17 was used for data analysis. P value < 0.05 was considered as statistically significant. RESULTS Of the 107 patients with IBS, 40 had positive GBT (37.4%) compared with 14 (12.1%) out of the 107 control participants(p< 0.001). Dominant symptoms in patients with IBS were diarrhea in 36(33.6%), constipation in 12(11.2%), abdominal pain in 22(20.6%), bloating in 28(26.2%), and change in bowel habit in 9(8.4%) patients. There was not statistically significant difference among any of this IBS subgroups and positive GBT (p=0.44). CONCLUSION There is a positive association between IBS and SIBO. We suggest a Placebo-controlled bacterial eradication study for identifying the role of SIBO in IBS.

Prevalence of narcotic bowel syndrome in opioid abusers in iran.

BACKGROUND In spite of the increasing trend in opioid abusers worldwide, the prevalence of narcotic bowel syndrome (NBS) is undetermined. We aimed to estimate the prevalence of NBS and other opioid bowel dysfunction (OBD) in opioid abusers in Kerman, southeast Iran. According to the best of our knowledge, this is the first study to assess the prevalence of NBS in opioid abusers. METHODS By referring to addiction treatment centers in Kerman city and in a cross-sectional study, 577 subjects with opium or opioid subtracts abuse were included in our study. A validated questionnaire was used for OBD assessment and diagnosis of NBS was made according to both the presence of chronic abdominal pain despite increasing the opioid dose and ruling out other causes of abdominal pain. SPSS software version 16 was used for data analysis. p value<0.05 was considered as statistically significant. RESULTS Constipation, regurgitation, and heartburn were the most gastrointestinal complaints that were found in 132(22.9%), 123(21.3%) and 91(15.8%) subjects, respectively. Only 16(2.8%) participants fulfilled all the NBS criteria. Simultaneous use of non-narcotic sedative drugs increased the risk of NBS significantly (the odds ratio 3:1 and p=0.049). CONCLUSION NBS is not rare among opioid abusers and should be considered as a cause of chronic abdominal pain in this group.

Fulminate hepatic failure as an initial presentation of non-hodgkin lymphoma: a case report.

Viral hepatitis and toxins comprise most common causes of fulminate hepatic failure that are often diagnosed with standard laboratory tests. Herein we discuss a rare, difficult to diagnosis etiology of acute liver failure (ALF). A 62-year-old man presented with a two-week history of fever and fatigue. At four days before admission he became lethargic. His past medical and drug histories were unremarkable. Physical examination revealed generalized jaundice, fever and loss of consciousness. Laboratory tests showed elevated liver transaminases with direct hyper-bilirubinemia. Abdominal ultrasonography and CT scan showed hepatosplenomegaly and para-aortic abdominal lymphadenopathy. A further work-up included liver biopsy. The histopathology and imunohistochemistry was compatible with diffuse large B-cell lymphoma. He underwent high dose glucocorticoid therapy but his condition deteriorated rapidly and he died eight days after admission. ALF as an initial manifestation of malignant hepatic infiltration is extremely rare yet should be considered in all patients with unknown hepatic failure that are highly suspicious for malignant neoplasm.

Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease.

BACKGROUND: Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). Adiponectin is a white and brown adipose tissue hormone, and have been found to play essential roles in the regulation of energy homoeostasis. Recent reports have identified a possible role of adiponectin in NAFLD via PPARγ pathway. OBJECTIVES: The present study was designed to find out the impact of adiponectin rs1501299 (276G/T) and rs266729 (-11377C/G) gene polymorphisms in NAFLD. PATIENTS AND METHODS: Eighty-three patients with diagnosis of NAFLD, and 93 healthy subjects were included in the study. Tetra ARMS-PCR was designed to detect single nucleotide polymorphisms. RESULTS: A significant difference was found between NAFLD and control group regarding the rs266729 polymorphism (χ2 = 7.35, P = 0.025). The rs266729 polymorphism increased the risk of NAFLD in codominant (CC vs. CG: OR = 2.18, 95% CI = 1.16 - 4.12, P = 0.016) and dominant (CC vs. CG/GG: OR = 2.31, 95% CI = 1.25 - 4.27; P = 0.008) inheritance tested models. The G allele increased the risk of NAFLD (OR = 1.63, 95% CI = 1.03 - 2.57, P = 0.037) in comparison with C allele. No significant difference was found between the groups concerning adiponectin rs1501299 gene polymorphism (χ2 = 0.70, P = 0.697). CONCLUSIONS: adiponectin rs266729 polymorphism might be a candidate gene, which determines the susceptibility to NAFLD. Larger studies are necessary to confirm these findings in various populations.

Serum paraoxonase and arylesterase activities in Iranian patients with nonalcoholic fatty liver disease.

BACKGROUND: The aim of the study was to investigate paraoxonase-1 (PON1) and aryl esterase (ARE) activities in patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This case-control study was done on 83 subjects with confirmed NAFLD (50 male, 33 female, age; 40.46±12.13 years) and 138 healthy individuals (75 male, 63 female; age; 40.94±14.50 years). PON1, salt-stimulated PON1 and ARE activities were determined using paraoxon and phenyl acetate as substrate, respectively. RESULTS: The levels of PON1 activities in NAFLD and healthy individuals were 90.83±63.65 IU/L and 79.41±68.14 IU/L, respectively. There was no significant differences regarding PON1 activity between NAFLD and healthy subjects (p=0.229). While, ARE activity was significantly higher in NAFLD (83.34±28.36 KU/L) than in normal subjects (64.06±27.49 KU/L) (p<0.001). CONCLUSIONS: Our results showed that PON1 activity is not a promising biomarker for the evaluation of NAFLD while arylesterase may have, but further studies in larger samples with different ethnic groups are required to validate our findings.

Association of genetic polymorphisms of glutathione-S-transferase genes (GSTT1, GSTM1, and GSTP1) and susceptibility to nonalcoholic fatty liver disease in Zahedan, Southeast Iran.

Oxidative damage is thought to play a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Glutathione-S-transferases (GSTs) are involved in cell protection against oxidative stress. We examined whether GSTM1, GSTT1, and GSTP1 polymorphisms are associated with NAFLD in a sample of the Iranian population. The current case-control study included 83 patients with NAFLD and 93 healthy subjects. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). The GSTP1 polymorphism was detected by tetra amplification refractory mutation system-PCR assay. The GSTM1-null genotype was significantly associated with the development of NAFLD (odds ratios [OR]=2.171, 95% confidence intervals [CI]=1.188-3.970, p=0.015). The GSTP1 Val allele was shown to be a risk factor for NAFLD (OR=1.739, 95% CI=1.089-2.777, p=0.024). The GSTT1 polymorphism was not significantly different between control and patient groups (p=0.221). This study showed that GSTM1 and GSTP1, but not GSTT1, genetic polymorphisms are associated with NAFLD in a sample of the Iranian population, and may be used to determine the risk of development of NAFLD.

Association of polymorphisms in glutamate-cysteine ligase catalytic subunit and microsomal triglyceride transfer protein genes with nonalcoholic fatty liver disease.

Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to examine the single nucleotide polymorphism (SNP) -129C/T (rs17883901) in glutamate-cysteine ligase catalytic subunit (GCLC) and SNPs I128T (rs3816873) and Q95H (rs61733139) in microsomal triglyceride transfer protein (MTTP) in NAFLD. Eighty-three patients with a diagnosis of NAFLD and 93 healthy subjects were included in the study. Tetra amplification refractory mutation system-polymerase chain reaction was designed to detect the SNPs. There were no significant differences in the polymorphism of -129C/T (rs17883901) of the GCLC gene among NAFLD and control groups (p > 0.05). A significant difference was observed between NAFLD and control group regarding the SNP I128T (rs3816873) in the coding region of the MTTP gene (p < 0.05). The CT genotype increased susceptibility to NAFLD (OR: 2.467; 95% CI: 1.253-4.854; p = 0.008). No significant difference was found among the groups regarding the SNP in the coding region of MTTP gene Q95H (rs61733139). In conclusion, MTTP rs3816873 polymorphism might be a candidate to determine susceptibility to NAFLD. Larger studies are necessary to confirm these findings in various populations.