Post-COVID-19 Syndrome Mechanisms, Prevention and Management.

As the population of patients recovering from COVID-19 grows, post COVID-19 challenges are recognizing by ongoing evidences at once. Long COVID is defined as a syndrome with a range of persistent symptoms that remain long after (beyond 12 weeks) the acute SARS-CoV-2 infection. Studies have shown that long COVID can cause multi-organ damages with a wide spectrum of manifestations. Many systems, but not limited to, including respiratory, cardiovascular, nervous, gastrointestinal, and musculoskeletal systems, are involved in long COVID. Fatigue and dyspnea are the most common symptoms of long COVID. Long COVID-19 may be driven by tissue damage caused by virus-specific pathophysiologic changes or secondary to pathological long-lasting inflammatory response because of viral persistence, immune dysregulation, and autoimmune reactions. Some risk factors like sex and age, more than five early symptoms, and specific biomarkers have been revealed as a probable long COVID predicator discussed in this review. It seems that vaccination is the only way for prevention of long COVID and it can also help patients who had already long COVID. Managing long COVID survivors recommended being in a multidisciplinary approach, and a framework for identifying those at high risk for post-acute COVID-19 must be proposed. Possible therapeutic options and useful investigation tools for follow-up are suggested in this review. In sum, as evidence and researches are regularly updated, we provide the current understanding of the epidemiology, clinical manifestation, suspected pathophysiology, associated risk factors, and treatment options of long COVID in this review.

Regulatory T-cell profile in early and late lesions of cutaneous leishmaniasis due to Leishmania major.

CONTEXT: Cutaneous leishmaniasis (CL) is a public health problem in several endemic countries. Recent studies on mouse model and also a few clinical experiments showed that the type of immune response generated at the site of infection and especially balance between regulatory and effector T-cells determines the outcome of the disease toward self-limiting or long-lasting lesions. AIMS: The aim of this study was to evaluate the role of natural regulatory T cells (nTregs) in early and late cutaneous lesions of human Leishmania major (L. major) infection. SETTINGS AND DESIGN: Skin biopsies were collected from parasitologically proven lesions of 28 CL patients, divided into two groups of early and late lesions. The causative agents were identified to be L. major. MATERIALS AND METHODS: Quantitative real-time reverse transcription polymerase chain reaction (PCR) and immunofluorescent staining of biopsies were used to assess the Foxp3 mRNA expression and frequency of nTregs in two groups. Mann-Whitney U test was used to determine the significance of deference between the two groups. RESULTS: Mean relative expressions of Foxp3 mRNA were 0.53 ± 0.23 and 1.26 ± 0.99 in early and late lesions, respectively, which was significantly upper in chronic lesions (P = 0.007). Parallel results were obtained in tissue staining method. CONCLUSIONS: Increased in gene expression and protein staining of nTreg markers in chronic biopsy samples indicates a role for these cells in chronic L. major induced leishmaniasis and supports the effectiveness of regulatory T cell-based immunotherapy for treatment of chronic CL.

Pharmacokinetics, Organ Toxicity and Antitumor Activity of Docetaxel Loaded in Folate Targeted Cholesterol Based Micelles.

BACKGROUND: To overcome insufficient concentration of chemotherapeutic drugs at tumor site and severe side effects in non-targeted tissues which limit their use targeting their overexpressed receptors represent a promising approach for cancer therapy. METHODS: The antitumor activity of docetaxel (DTX) loaded in folate targeted Synpronic F127- Cholesterol (FA-PF127-Chol) nanomicelles was evaluated in C57BL6 mice bearing melanoma and their survival was studied. The pharmacokinetic of DTX loaded FA-PF127-Chol micelles in comparison with Taxoter(®) was investigated in male Wistar rats. The tumor proliferation was detected by Ki67 assay. The systemic organ toxicity was evaluated in healthy bulb-c mice. RESULTS: DTX loaded FA-PF127-Chol micelles significantly inhibited tumor growth and enhanced animal survival compared to Taxoter(®) and non-targeted micelles. FA-PF127-Chol micelles significantly enhanced mean residence time (MRT) and AUC0-∞ of DTX compared to Taxoter(®). The immunehistochemical study demonstrated that DTX loaded FA-PF127-Chol significantly inhibited intra-tumoral cell proliferation in comparison with other treated groups. Safety evaluation showed no toxicity of DTX loaded targeted micelles on blood cells. Histopathology analysis of major organs of mice treated with DTX loaded FA-PF127-Chol micelles showed less tissue damages compared to Taxoter(®) and non-targeted ones. DISCUSSION: The results of this contribution showed the potential of DTX loaded FA-PF127-Chol in treatment of melanoma.

A comparison of peroxisome proliferator-activated receptor-α agonist and antagonist on human umbilical vein endothelial cells angiogenesis.

BACKGROUND: There are controversial reports about the antiangiogenic effects of peroxisome proliferator-activated receptor α (PPARα). In the current study, we compared the effects of PPARα agonist and antagonist on human umbilical vein endothelial cells (HUVECs) angiogenesis with matrigel assay. MATERIALS AND METHODS: HUVECs (1 × 10(5) cells/well) treated with PPARα agonist (fenofibrate) and antagonist (GW6471) were cultured on matrigel for 24 h. Treated cells were stained with calcein and investigated by fluorescent microscopy. The obtained images were also analyzed by AngioQuant software. Finally, the data were analyzed using SPSS 15 software, Kruskal-Wallis and one way ANOVA. RESULTS: Statistical analysis showed that fenofibrate significantly inhibit the tube formation (size, length, junction) (P < 0.05) but there was a trend to increased angiogenesis in GW6471 treated group (P > 0.05). CONCLUSION: These results showed that PPARα agonist is effective in suppression of angiogenesis. Further studies are needed to confirm these results in in vivo studies.

Effects of different doses of doxepin on passive avoidance learning in rats.

BACKGROUND: Studies have shown that Doxepin has anti-inflammatory effects and reduces oxidative stress. Due to the fact that other tricyclic antidepressants have been shown to have neuroprotective effects, this study aimed to investigate the effects of different doses of doxepin on passive avoidance learning in rats. MATERIALS AND METHODS: Old male Wistar rats were used in this study. Doxepin was administered intraperitoneally (1, 5 and 10 mg/kg) for 21 days. Passive avoidance learning test was used for evaluation of learning and memory. Rats received foot electrical shock on fifteen day, and step through latencies were evaluated one week after the electrical shock in retention phase. RESULTS: Administration of Doxepin considerably increased the step through latencies in the rats that received the doses of 1 and 5 mg/kg (P < 0.05). However, in the dose of 10 mg/kg, there wasn't any significant change comparing to control group. CONCLUSION: These results indicate that Doxepin has desirable effects on cognitive functions in low doses. Therefore, Doxepin can be considered as memory enhancers that understanding the underling mechanisms need further investigation.

The effects of blocking Angiotensin receptors on early stages of diabetic nephropathy.

BACKGROUND: This study aimed to investigate the beneficial effects of angiotensin receptor blockers (ARBs) on markers of endothelial function in patients with early stage of diabetic nephropathy (DN). METHODS: This cross-sectional study was conducted on 32 participants with IDDM from January 2010 until May 2011 in Isfahan, Iran. The participants were candidate for receiving ARBs or angiotensin-converting enzyme inhibitors (ACEIs) to decrease microalbuminuria. The inclusion criteria were as follows: the age of onset of insulin-dependent diabetes mellitus (IDDM)less than 15 years; normal glomerular filtration rate (GFR); normal blood pressure; normal cardiovascular examination; negative urine culture, receiving no medications except insulin. Microalbuminuria was measured in two fasting urine samples with a sampling interval of at least 1-2 months by ELISA method. Patients with two abnormal results were included. Microalbumin to creatinin ratio equal to or more than 30 mg/gm was considered abnormal. The fasting blood samples to determine serum nitric oxide (NO) and vascular cell adhesion molecule (VCAM) were obtained at the time 0 (before starting the study), and after 2 months of receiving ARBmedication. Valsartan tablet (Diovan, Novartis Company) with a dose of 1 mg/kg/day up to 80 mg/day in a single dose was administered. RESULTS: Urine microalbumin to creatinin ratio after valsartan consumption was lower than microalbumin level before the medication, P < 0.05. After valsartan consumption, serum VCAM-1 level reduced and NO level increased significantly, P < 0.05. CONCLUSION: Angiotensin receptor blockers may reduce VCAM-1 and microalbuminuria and may increase NO levels in early stages of DN. Thus administration of ARBs might be considered even in early stages of DN.