Immunosuppression is a Double-Edged Sword in COVID-19 Treatment: a Case Report of Rhino-Orbito-Cerebral Mucormycosis.

BACKGROUND: Mucormycosis is a life-threatening fungal infection mostly occurring in immunosuppressed patients such as organ transplant or diabetic patients. In this paper, we described a case of COVID-19 with rhino-orbito-cerebral mucormycosis. METHODS: The nucleic acid amplification test (NAAT) from a nasopharyngeal sample for SARS-CoV-2 was done. Demographic data, biochemical tests, paranasal sinuses (PNS) CT scan, brain CT scan, chest CT scan, and palate biopsy were performed. RESULTS: The NAAT was positive for SARS-CoV-2. PNS CT scan revealed mucosal thickening of all paranasal sinuses, brain CT scan showed hypodense area in antero-inferior cortex, and chest CT scan revealed diffuse ground glass opacity in favor of COVID-19 infection. Palate biopsy revealed fibroconnective tissue with broad pauciseptated ribbon-like hyphae. CONCLUSIONS: In this paper, a case of COVID-19 with rhino-orbito-cerebral mucormycosis was described. The treatment with immunosuppressive drugs predisposed this patient to secondary fungal infection. Immunosuppression is a double-edged sword in COVID-19 treatment and immunosuppressive drugs should be prescribed only in severely ill patients and for a short period.

Effect of Pentoxifylline on Inflammatory Cytokines, Adequacy of Dialysis, Anemia and Biochemical Markers of Hemodialysis Patients: a Randomized Controlled Trial.

BACKGROUND: The main cause of death in hemodialysis patients is cardiovascular disease (CVD). Chronic inflammation is strongly related with CVD, atherosclerosis, and malnutrition in end-stage renal disease (ESRD) patients. We aimed to investigate the effect of pentoxifylline on adequacy of dialysis, anemia, inflammatory cytokines, and biochemical markers in patients with ESRD on hemodialysis. METHODS: This was a randomized controlled trial with a negative result conducted on 42 hemodialysis patients. The patients were randomly divided to two groups; intervention group (400 mg pentoxifylline every night for three months) and control group (followed up without taking pentoxifylline). The blood samples were taken to measure the levels of inflammatory cytokines, anemia-related parameters, and biochemical markers at baseline and the end of treatment. RESULTS: Thirty-six patients finished the study (18 patients in each group). There was significant reduction in C-reactive protein (CRP) [9.25 (4.60, 17.62) vs. 5.60 (1.90, 11.52), p = 0.048] and TNF-α [28.06 (19.76, 61.22) vs. 18.06 (14.39, 28.97), p = 0.029], and significant increase of albumin levels (4.05 ± 0.25 vs. 4.35 ± 0.24, p = 0.000) in the intervention group, but these changes were not significant in comparison with the control group. No statistically significant difference was observed between intervention and control groups in other parameters. CONCLUSIONS: Although pentoxifylline administration had caused significant reduction in CRP and TNF-α, as well as significant increase of albumin levels in the intervention group, but these changes were not significant in comparison with control group. The current study does not support the use of pentoxifylline in hemodialysis patients.

Decreased Plasma Level of TRIB3 is Associated with Circulating miR-124a in Patients with Type 2 Diabetes.

BACKGROUND: Recent evidence indicates that TRIB3 and miR-124 levels have been deregulated in type 2 diabetes (T2D); however, the simultaneous evaluation of these markers in diabetic patients has not been investigated to date. METHODS: This case-control study included 50 T2D patients and 40 age-gender matched controls. The circulation level of miR-124a was assessed by real-time PCR. TRIB3 plasma level was measured using the enzyme-linked im-munosorbent assay. RESULTS: Our findings revealed that the TRIB3 plasma level was significantly increased (p = 0.025), while miR-124a plasma levels were significantly reduced (p = 0.028) in diabetic patients compared to healthy subjects. ROC analysis showed that TRIB3 and miR-124a levels could discriminate control subjects and diabetic patients. Interestingly, a significant negative correlation was found between the TRIB3 and miR-124a plasma levels. Furthermore, there was a significant positive correlation between the TRIB3 plasma level with fasting blood glucose and insulin resistance. CONCLUSIONS: In this study, we showed deregulation of TRIB3 level in diabetic patients and its association with miR-124a circulating level and clinical parameters. These findings suggest that miR-124a may affect T2D incidence and progression by modulating the expression of TRIB3 protein level.

Plasma Levels and Gene Expression of RANK in Non-Alcoholic Fatty Liver Disease.

BACKGROUND: The pathobiology of initiation and progression of nonalcoholic fatty liver disease (NAFLD) has not been completely elucidated. It seems that the RANK/RANKL/OPG cytokine system play an etiologic role in pathogenesis of this disease. This study aimed to investigate the plasma content and gene expression of RANK in NAFLD patients as compared to healthy individuals. METHODS: This case-control work was performed on 63 patients with NAFLD and 25 healthy subjects. The plasma levels of RANK and biochemical parameters were measured using ELISA and colorimetric methods, respectively. Also, RANK mRNA content was evaluated by quantitative RT-PCR in peripheral blood mononuclear cells. RESULTS: RANK plasma contents were shown to be lower in NAFLD patients than in control subjects (1.02 ± 0.75 and 1.41 ± 1 ng/mL, respectively (p = 0.008)). The differences in gene expression of RANK between NAFLD patients and controls were significant (p = 0.001). In the NAFLD patients, RANK was inversely correlated with HDL. Logistic regression showed the association of RANK plasma content with the risk of NAFLD. Moreover, ROC curve analysis showed that RANK has a great ability to differentiate between NAFLD patients and controls. CONCLUSIONS: This study for the first time showed lower plasma and mRNA levels of RANK in NAFLD patients compared to control individuals. These results recommend a possible association between RANK and pathobiology of NAFLD.

Malvidin prevents lipopolysaccharide-induced oxidative stress and inflammation in human peripheral blood mononuclear cells.

It is indicated that malvidin has anti-inflammatory and antioxidant effects on various cells, although the function of malvidin in preventing inflammatory reactions caused by lipopolysaccharide (LPS) in peripheral blood mononuclear cells (PBMCs) is still not known. The objective of this study was to examine the impact of malvidin on inflammatory responses and oxidative stress in PBMCs as caused by LPS. The present findings showed that LPS significantly increased the expression of IL-6, TNF-α, IL-1ß, and COX-2 mRNA and protein release from PBMCs 22 hr after treatments. It was also revealed that increased levels in cytokine expression coincided with increased phosphorylation of JNK, P65-NF-κB, and IKKα/IKKß. Also, the expression of IL-6, TNF-α, IL-1ß, and COX-2 mRNA induced by LPS as well as secretion of protein in PBMC has been significantly decreased by pretreatment of malvidin. Importantly, pretreatment of the cells with malvidin completely abrogated the phosphorylation of P65-NF-κB, JNK, and IKKα/IKKß in LPS treated cells. Malvidin protection against LPS-induced inflammation was coupled with a decline in the levels of nitric oxide metabolite and malondialdehyde, along with an increase in the ferric reducing antioxidant power, total thiol activity, and also superoxide dismutase and glutathione peroxidase activity. In accordance with this finding, malvidin may represent a promising therapeutic agent for the prevention of inflammation in PBMCs.

Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor-α-related protein-6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf-PCOS] and PCOS-RPL). This case-control study included 120 PCOS patients (60 inf-PCOS and 60 PCOS-RPL) and 60 healthy controls. Serum high-sensitivity C-reactive protein (hs-CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf-PCOS and PCOS-RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs-CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs-CRP in PCOS group and inf-PCOS subgroup, but not PCOS-RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.

Extraction and Identification of Two Flavonoids in Phlomoides hyoscyamoides as an Endemic Plant of Iran: The Role of Quercetin in the Activation of the Glutathione Peroxidase, the Improvement of the Hydroxyproline and Protein Oxidation in Bile Duct-Ligated Rats.

BACKGROUND: Cholestatic liver disease, a serious chronic condition that develops progressive hepatic degeneration through free radicals. OBJECTIVE: The present study was designed to extract and identify two flavonoids in Phlomoides hyoscyamoides plant, native to Iran and evaluate the role of quercetin identified on the liver injury among bile ductligated rats. METHODS: This study was conducted on 25 male Wistar rats within three groups of sham control, mere bile duct-ligated, and bile duct-ligated with quercetin. The bile duct-ligated animals received quercetin at a dose of 50 mg/kg/day for 10 days, followed by biochemical tests, oxidative stress markers, activity of antioxidant enzymes and hematoxylin and eosin staining. Molecular docking was used to explore the interactive behavior of quercetin with glutathione peroxidase. RESULTS: According to analyses of the obtained extract, two main active ingredients of P. hyoscyamoides were rutin and quercetin. Bile duct-ligated group showed a significant liver necrosis, a clear increase in plasma and tissue oxidative stress parameters, and a decrease in glutathione peroxidase activity as compared to sham control group. Quercetin injection in bile duct-ligated rats resulted in significant decrease in hydroxyproline, protein carbonyl and histopathologic indexes and significant increase in glutathione peroxidase activity (P-value≤0.05). Based on the molecular docking, the quercetin was able to regulate the glutathione peroxidase activity. CONCLUSION: The quercetin acts as an enzyme inducer by renewing the glutathione peroxidase activity and inhibiting the oxidation of proteins and hence decreases the oxidative stress. These results could be a sign of confirming the positive role of quercetin in attenuating the liver damage and degeneration.