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The reproductive system of males is adversely impacted by lead (Pb), a toxic heavy metal. The present study examined arbutin, a promising hydroquinone glycoside, for its potential ameliorative impact against Pb-induced testicular impairment in rats. The testicular injury was induced by the intraperitoneal administration of Pb acetate (20 mg/kg/day) for 10 consecutive days. Thirty-six rats were divided into six experimental groups (n = 6 per group): control, control treated with oral arbutin (250 mg/kg), control treated with intraperitoneal arbutin (75 mg/kg), untreated Pb, Pb treated with oral arbutin, and Pb treated with intraperitoneal arbutin. The treatments were administered daily for 10 days. Arbutin was administered by the oral and intraperitoneal routes to compare the efficacy of both routes in mitigating Pb acetate-induced testicular dysfunction. The current data revealed that both oral and intraperitoneal administration of arbutin significantly enhanced serum testosterone and sperm count/motility, indicating the amelioration of testicular dysfunction. In tandem, both routes lowered testicular histopathological aberrations and Johnsen's damage scores. These favorable outcomes were driven by dampening testicular oxidative stress, evidenced by lowered lipid peroxidation and increased glutathione and catalase antioxidants. Moreover, arbutin lowered testicular p-JAK2 and p-STAT3 levels, confirming the inhibition of the JAK2/STAT3 pro-inflammatory pathway. In tandem, arbutin suppressed the testicular NLRP3/caspase-1/NF-B axis and augmented the cytoprotective PK2/PKR2 pathway. Notably, intraperitoneal arbutin at a lower dose prompted a more pronounced mitigation of Pb-induced testicular dysfunction compared to oral administration. In conclusion, arbutin ameliorates Pb-evoked testicular damage by stimulating testicular antioxidants and the PK2/PKR2 pathway and inhibiting the JAK2/STAT3 and NLRP3/caspase-1 pro-inflammatory pathways. Hence, arbutin may be used as an adjunct agent for mitigating Pb-induced testicular impairment.
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Background: Extreme body mass index (BMI) is an influential pathophysiological risk factor for serious illnesses following lower respiratory tract infection. The purpose of the current study was to examine how the BMI of Coronavirus disease-19 (COVID-19) patients affects their prognosis. Methods: Two hundred patients with COVID-19 admitted to Al-Azhar, Qena, Aswan, and Sohag University hospitals in Egypt were included and categorized into four groups according to their BMI. The diagnosis was made according to a real-time reverse transcription-polymerase chain reaction (rRT-PCR) positive result for the SARS-CoV-2 nucleic acid in swabs from upper respiratory tract. A detailed history, clinical examination, and outcomes (disease severity and complications, hospital stay, ICU admission, mortality) were recorded for all patients. SPSS version 24 software was used for data analysis. Results: Average age of participants (19-90 years old), 92 (46%) males and 108 females (54%). ICU admission was significantly higher among underweight patients (75%) and obese patients (78.6%). The majority of underweight (62.5%) and obese (57.1%) patients had critical disease. Invasive mechanical ventilation (MV) is frequently used in underweight (50%) and obese patients (42.9%) patients. Adult respiratory distress syndrome (ARDS), cardiac, neurological, and hematological complications, and incidence of myalgia and bed sores were most frequent among obese and overweight patients. Acute kidney injury was significantly higher among underweight patients (37.5%) and obese patients (28.6%) than among other classes (p=0.004). Frequency of endocrine complications was significantly higher in underweight patients than that in other classes (p=0.01). The majority of underweight (75%) and obese patients (50%) deteriorated and died, whereas the majority of normal-weight patients (90.3%) and overweight patients (75.8%) improved and were discharged (p< 0.001). Conclusion: Body mass index is a major contributing factor to the outcome of patients with COVID-19, and patients with extreme of body mass index were associated with the worst prognosis.
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Aim of the study: To evaluate the role of MIF gene polymorphism rs755622 G>C in occurrence and progression of hepatocellular carcinoma (HCC) among a cohort of Egyptian patients. Material and methods: This case-control study was conducted on 50 patients with HCC after chronic viral hepatitis and 50 healthy volunteers, recruited between July 2021 and January 2022. All patients with HCC were evaluated for severity of liver disease using a Child-Pugh score, and TNM and BCLC scoring systems. MIF 173 G>C (rs755622) single nucleotide polymorphism was performed for all participants by polymerase chain reaction using restriction fragment length polymorphism technique (RFLP-PCR). Results: Overall results showed significantly higher frequencies of GG (wild homozygous genotype) and mutant heterozygous genotype GC and G allele (OR = 6.303, 95% CI: 3.374-11.775) among patients with HCC compared to the control group (p = 0.001) for all. Also, significantly higher frequency of genotype GG was detected among patients with advanced Child scores (B and C) (p = 0.039) and TNM stages (III and IV) (p = 0.013). There was significantly higher frequency of the G allele among patients with multiple hepatic focal lesions compared to those with a single focal lesion (p = 0.01). Conclusions: An obvious role of MIF (rs755622) gene polymorphism could have an important role in susceptibility and progression of HCC among patients with chronic viral hepatitis induced liver cirrhosis.
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Introduction: HCC is frequently diagnosed late, when only palliative treatment is available. So, we try to use different immunological markers to identify early HCC in patients with unremarkable raised AFP. Methods: This study was conducted on 112 participants divided into two equal groups: Group I, 56 patients with liver cirrhosis and different stages of HCC; Group II, 56 patients with liver cirrhosis. The diagnosis of HCC was based on AASLD guidelines. TNM and BCLC classification systems are used for staging of HCC. Results: A significant reduction in the median percentage of lymphocyte subset (CD3+, CD4+, CD8+, CD19+) and NK cell percentage (CD56+) has been detected in HCC patients (all P < 0.001). In the HCC group the median monocyte subpopulations CD14+ CD16- Classical, CD14++ CD16+ Intermediate, and CD14-+ CD16++ Non-Classical were 11.7, 4.0, and 3.5, respectively, with marked reduction compared with liver cirrhosis group (all P < 0.001). Patients with advanced stages (BCLC C and D) were more likely to have significantly higher median CD33+ than patients with early stages (BCLC A and B) (P = 0.05); also, the median levels of HLA DR+ lymphocytes % in the HCC case group were 21.8 in patients with advanced disease (BCLC C and D) and 13.1 in patients with early stages of the disease (P = 0.04). Patients with late stage (TNM III) were more likely to have significantly higher median CD14+ CD16- Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16- than patients with early stages (TNM I and II). Conclusion: Patients with HCC with unremarkable raised AFP showed marked reduction in lymphocytes, natural killer cells, and all monocyte subpopulations. In addition, patients with advanced HCC showed increased CD33+ and HLA DR+ lymphocytes %, CD14+ CD16- Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16- compared with patients with early stages of HCC.
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Background: Obesity is a significant public health problem that is characterized by an increase in oxidative stress and enhanced inflammatory responses associated with immune cell invasion of adipose tissues. This study assessed several biochemical abnormalities, apoptosis, oxidative stress status, and associated histological changes in the liver, duodenum, and heart brought on by high-fat diet-induced obesity in rats. It also assessed the mechanistic benefits of curcumin in reversing these inflammatory, metabolic, and histological impairments. Methods: Rats were assigned into three groups each including ten rats: the control group (CD), the high-fat diet group (HFD), and the high-fat diet + curcumin (HFDC) group. Serum glucose, insulin, and triglycerides (TAGs) were observed. In addition, apoptosis (indicated by hepatic DNA fragmentation) and oxidative stress status (indicated by hepatic MPO, GSH, and SOD) were assessed. Histopathological examinations included the GIT (liver and duodenum) and heart in addition to quantitative real-time polymerase chain reaction (qRT-PCR) assays of the adipose tissue genetic expressions for inflammatory signaling pathways (TLR4, IL-6, and TNF-α). Results: The overall findings showed that the HFD group exhibited significantly higher levels of glucose, TAGs, and insulin than the control group (P < 0.01). The histological abnormalities of the studied organs in the HFD group were paralleled by these biochemical abnormalities, which were strongly associated with increased apoptosis, increased oxidative stress, and increased expression of the inflammatory signaling markers. There were significant improvements in the HFDC group in terms of biochemical, inflammatory, and histological investigations. Conclusions: This study's findings concluded that obesity is significantly associated with biochemical and microscopic alterations in many organs. Curcumin exerted potent antitoxic, antioxidant, tissue-protective, and antiobesity effects. Curcumin is recommended to be added to various dietary regimens to prevent or delay the organs' dysfunction among obese people.
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Osteoarthritis (OA) etiology and pathogenesis not yet fully understood. We studied the role of vitamin D receptor single-nucleotide polymorphisms (VDR-SNPs), vitamin D3, serum and synovial macrophage migration inhibitory factor (MIF), and tumor necrosis factor-α (TNF-α) in the development and progression of knee OA (KOA). This study included 205 Egyptian subjects (105 patients with KOA and 100 unrelated, healthy matched subjects selected as controls). The patient group was divided into three groups according to KOA severity (mild, moderate, and severe), with 35 patients in each group. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for the ApaI and TaqI SNPs. Vitamin D, serum and synovial TNF-α, and MIF assays were performed using ELISA kits. There were significantly lower serum levels of 25-hydroxycholecalciferol with significant increasing TNF-α and MIF levels in relation to disease severity among the cases (all: pË0.05).Wild homozygous and heterozygous mutant genotypes (GG+GT) and G allele of ApaI demonstrated risk for KOA development, with odds ratio OR = 6.313 (95% confidence interval (CI) 2.074-19.210) and OR = 1.532 (95%CI 1.013-2.317), respectively. Homozygous mutant CC genotype and C allele of TaqI could be considered a risk factor associated with KOA development, with OR = 2.667 (95%CI 1.270-5.601) and OR = 0.737 (95%CI 0.496-1.095), respectively. VDR-SNPs, vitamin D3, TNF-α, and MIF could play an essential role in the pathogenesis and progression of KOA with mechanistic associations.