Exploring the role of tryptophanyl-tRNA synthetase and associations with inflammatory markers and clinical outcomes in COVID-19 patients: A case-control study.

Tryptophanyl-tRNA synthetase (WRS) is a critical enzyme involved in protein synthesis, responsible for charging tRNA with the essential amino acid tryptophan. Recent studies have highlighted its novel role in stimulating innate immunity against bacterial and viral infections. However, the significance of WRS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains elusive. In this study, we aimed to investigate the complex interplay between WRS, inflammatory markers, Toll-like receptor-4 (TLR-4), and clinical outcomes in coronavirus disease 19 (COVID-19) patients. A case-control investigation comprised 127 COVID-19 patients, carefully classified as severe or moderate upon admission, and 112 healthy individuals as a comparative group. Blood samples were meticulously collected before treatment initiation, and WRS, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were quantified using a well-established commercial ELISA kit. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples, and RNA was extracted for cDNA synthesis. Semi-quantitative real-time polymerase chain reaction (PCR) was employed to assess the relative expression of TLR-4. COVID-19 patients exhibited elevated levels of WRS, IL-6, CRP, and TLR-4 expression compared to healthy individuals, with the severe group displaying significantly higher levels than the moderate group. Notably, severe patients demonstrated substantial fluctuations in CRP, IL-6, and WRS levels over time, a pattern not observed in their moderate counterparts. Although no significant distinctions were observed in the dynamic alterations of WRS, IL-6, CRP, and TLR-4 expression between deceased and surviving patients, a trend emerged indicating higher IL-6_1 levels in deceased patients and elevated lactate dehydrogenase (LDH) levels in severe patients who succumbed to the disease. This pioneering research highlights the dynamic alterations of WRS in COVID-19 patients, providing valuable insights into the correlation between WRS, inflammatory markers, and disease severity within this population. Understanding the role of WRS in SARS-CoV-2 infection may open new avenues for therapeutic interventions targeting innate immunity to combat COVID-19.

Programmed Death 1 (PD-1) Expression in Relapsing and Remitting Hodgkin Lymphoma as Prognostic Factor.

BACKGROUND: Programmed death ligand 1 (PD-L1) plays critical role in PD-1-dependent immunity suppress. Abnormal PD-L1 expression has shown to be directly related to poor prognosis and drug resistance in cancer patients. Hence, we aimed to evaluate PD-L1 expression in relapsing and remitting Hodgkin lymphoma (HL) as a prognostic factor. METHODS: In this cross-sectional study, 100 patients with HL between 2007 and 2015, were included. A thin section of tumor tissue fixed and processed on slides, stained by immunohistochemistry (IHC) PD-L1 specific antibodies. The clinical, imaging and pathology information of patients were obtained using case reading and by retrospective follow-up. The status of recurrence or improvement was determined after 5 years of diagnosis. GraphPad Prism v.8 was used for analysis. RESULTS: of 100 HL cases, the mean age of 33 relapsed group cases was significantly higher than remission group (p-value = 0.006), and gender was not significant however majority of cases in both groups were male. The frequency of PD-L1 expression found in 49% of all patients. A significant relationship was found between the expression of PD-L1 and disease progression, HL subtype, stage of tumor (p-value<0.05). High expression of PD-L1 found in majority of relapse group and low expression in remission group. CONCLUSION: PD-L1 expression assessment in HL patients is a valuable tool for prediction of the disease subtype, progression, stage, and treatment outcome. IHC method as an available, simple, rather cheap, and efficient tool could use for evaluation of PD-L1 expression and predicting the prognosis of HL disease, elsewhere.

Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors.

DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. Several studies showed that the dysregulation of DDIT4 is involved in different malignancies with paradoxical expressions and roles. Therefore, this study investigated the clinical significance, prognostic, and diagnostic value of DDIT4 in different types of pancreatic tumors (PT). The expression of DDIT4 and long non-coding RNA (TPTEP1) in mRNA level was examined in 27 fresh PT samples using Real-time quantitative PCR (RT-qPCR). Moreover, 200 formalin-fixed paraffin-embedded PT tissues, as well as 27 adjacent normal tissues, were collected to evaluate the clinical significance, prognostic, and diagnosis value of DDIT4 expression by immunohistochemistry (IHC) on tissue microarrays (TMA) slides. The results of RT-qPCR showed that the expression of DDIT4 in tumor samples was higher than in normal samples which was associated with high tumor grade (P = 0.015) and lymphovascular invasion (P = 0.048). Similar to this, IHC findings for nucleus, cytoplasm, and membrane localization showed higher expression of DDIT4 protein in PT samples rather than in nearby normal tissues. A statistically significant association was detected between a high level of nuclear expression of DDIT4 protein, and lymphovascular invasion (P = 0.025), as well as advanced TNM stage (P = 0.034) pancreatic ductal adenocarcinoma (PDAC) and in pancreatic neuroendocrine tumor (PNET), respectively. In contrast, a low level of membranous expression of DDIT4 protein showed a significant association with advanced histological grade (P = 0.011), margin involvement (P = 0.007), perineural invasion (P = 0.023), as well as lymphovascular invasion (P = 0.005) in PDAC. No significant association was found between survival outcomes and expression of DDIT4 in both types. It was found that DDIT4 has rational accuracy and high sensitivity as a diagnostic marker. Our results revealed a paradoxical role of DDIT4 expression protein based on the site of nuclear and membranous expression. The findings of this research indicated that there is a correlation between elevated nuclear expression of DDIT4 and the advancement and progression of disease in patients with PT. Conversely, high membranous expression of DDIT4 was associated with less aggressive tumor behavior in patients with PDAC. However, further studies into the prognostic value and biological function of DDIT4 are needed in future studies.

Simultaneous Bilateral Testicular Metastases from Renal Clear Cell Carcinoma: A Rare Presentation in Von Hippel-Lindau disease.

In this article, we present a Von Hippel-Lindau (VHL) patient with synchoronus bilateral testicular metastasis from renal cell carcinoma (RCC). A 50 year-old man, a known case of VHL syndrome was referred with palpable masses in both the testes. His medical history demonstrated that he had undergone the brain surgery for cerebellar hemangioblastoma. He had undergone simultaneous Whipple's pancreatectomy and left radical nephrectomy becuase of well-differentiated neuroendocrine tumors in head and body of the pancreas and a 6-cm clear cell-type grade-3 RCC in the left kidney. Scrotal sonography demonstrated vascular and heteroechogen masses measuring 19×14 mm in lower pole of the right testicle, 19×16 mm in upper pole of the right testicle, and 23×16.5 mm in upper pole of the left testicle. After having patient's consent, bilateral orchiectomy was performed by inguinal incision. Histopathologic examination and immunohistochemistry staining revealed metastasis from RCC. The most common neoplasm of reproductive system in VHL patients is epididymal papillary cystadenoma. Owing to it's benign nature, the management is conservative with routine physical examination and ultrasonography. Our patient indicated that every scrotal mass in patients with VHL is not to be considered as epididymal papillary cystadenoma.

A systematic update to circulating extracellular vesicles proteome; transcriptome and small RNA-ome as glioma diagnostic, prognostic and treatment-response biomarkers.

Brain gliomas are major neurosurgical challenges due to high mortality and morbidity. Hence, development of novel biomarkers is of great value to plan appropriate treatment strategy. Evaluation of the molecular content of extracellular vesicles (EVs) as novel non-invasive biomarker repertoires can provide a real-time portrait of disease status. This study aims to provide a systematic, comprehensive and critical report of the diagnostic and prognostic significance of EV biomarkers (proteins, DNAs and RNAs) for brain gliomas, discuss their biogenesis and passage through the blood brain barrier, and also highlight the high throughput methods used for EV biomarker discovery; as well as discussing potential limitations of EV isolation and characterization methods as glioma diagnostic, prognostic or treatment response biomarkers. Moreover, we critically appraise the bias risk in the previous studies, discuss the limitations EV biomarker discovery faces to enter neurosurgical practice in the future, and highlight the need for more optimized protocols for EV isolation and biomarker discovery in high throughput studies. The current systematic review was conducted upon PRISMA guidelines [10].

Distribution of human papillomavirus genotypes in suspected women cytological specimens from Tehran, Iran.

Background and Objectives: The human papillomavirus (HPV) is associated with more than 70% of the cervical neoplasm. The current study aims to evaluate the distribution of HPV genotypes in suspected women cytological specimens from Tehran, Iran. Materials and Methods: In the current cross-sectional study, HPV genotype prevalence was investigated in 433 subject women. DNA extraction was performed by High Pure Viral Nucleic Acid kit. A semi-automatically hybriSpot 24™ (HS24) setting was used for HPV typing and data interpreted by hybriSoft™ software according to instructions. Results: Pathologic data showed 181 (41.8%) had non-malignant lesions, 212 (49%) had inflammation and 40 (9.2%) reported LSIL in primary Pap-smear result. HPV was found in 143 (33%) specimens and the most comment high-risk and low-risk HPV types were HPV-16 and -6, respectively. Also, 62 (43%) were co-infected with multiple genotypes includes, 34 (24%) cases had co-infection with two HPV types, 17 (12%) cases had co-infection with three HPV types, 6 (4%) cases had co-infection with four HPV types and 5 (3%) cases had co-infection with five HPV types. There was statistically different domination on high-risk genotype in most of the co-infected samples (p<0.01). Conclusion: Current study indicates that the lesion pathology assessment was significantly associated with the HPV infection (p<0.01). Furthermore, the age group assessment shows that most of the HPV positive cases were 21 to 40 (p<0.01). The HPV infection prevalence in the current study was 33% and the most frequently reported high-risk and low-risk HPV types were 16 and 6, respectively.

Angioregulatory role of miRNAs and exosomal miRNAs in glioblastoma pathogenesis.

Glioblastoma (GB) is a highly aggressive cancer of the central nervous system, occurring in the brain or spinal cord. Many factors such as angiogenesis are associated with GB development. Angiogenesis is a procedure by which the pre-existing blood vessels create new vessels that play an essential role in health and disease, including tumors. Also, angiogenesis is one of the significant factors thought to be responsible for treatment resistance in many tumors, including GB. Hence, an improved understanding of the molecular processes underlying GB angiogenesis will pave the way for developing potential new treatments. Recently, it has been found that microRNAs (miRNAs) and exosomal miRNAs have a crucial role in inducing or inhibiting the angiogenesis process in GB development. A better knowledge of the miRNA's regulation pathway in the angiogenesis process in cancer offers unique mechanistic insight into the mechanism of tumor-associated neovascularization. Because of advancements in miRNA characterization and delivery methods, miRNAs can also be employed in clinical settings as potential biomarkers for anti-angiogenic treatment response as well as therapies targeting tumor angiogenesis. The recent finding and insights about miRNAs' angioregulatory role and exosomal miRNAs in GB are provided throughout the review. Also, we discuss the new concept of miRNAs-based therapies for GB in the future.

Dual role of microbiota-derived short-chain fatty acids on host and pathogen.

A growing body of documents shows microbiota produce metabolites such as short-chain fatty acids (SCFAs) as crucial executors of diet-based microbial influence the host and bacterial pathogens. The production of SCFAs depends on the metabolic activity of intestinal microflora and is also affected by dietary changes. SCFAs play important roles in maintaining colonic health as an energy source, as a regulator of gene expression and cell differentiation, and as an anti-inflammatory agent. Additionally, the regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. This review will present data supporting the diverse functional roles of microbiota-derived butyrate, propionate, and acetate on host cellular activities such as immune modulation, energy metabolism, nervous system, inflammation, cellular differentiation, and anti-tumor effects, among others. On the other hand, we will discuss and summarize data about the role of these SCFAs on the virulence factor of bacterial pathogens. In this regard, receptors and signaling routes for SCFAs metabolites in host and pathogens will be introduced.

Management of Pyogenic Granulomas Following Burn Wounds.

Pyogenic granuloma following burns (PGB) manifest in patients with different clinical and pathological features which is completely different with classic pyogenic granuloma. Up to now, there is no conclusive theory about presents of PG and its accurate etiology. This is a short brief about a 49-yr-old female with, TBSA 1% which PG develop on her burned area after 2 weeks.

Role of microbiota-derived short-chain fatty acids in nervous system disorders.

During the past decade, accumulating evidence from the research highlights the suggested effects of bacterial communities of the human gut microbiota and their metabolites on health and disease. In this regard, microbiota-derived metabolites and their receptors, beyond the immune system, maintain metabolism homeostasis, which is essential to maintain the host's health by balancing the utilization and intake of nutrients. It has been shown that gut bacterial dysbiosis can cause pathology and altered bacterial metabolites' formation, resulting in dysregulation of the immune system and metabolism. The short-chain fatty acids (SCFAs), such as butyrate, acetate, and succinate, are produced due to the fermentation process of bacteria in the gut. It has been noted remodeling in the gut microbiota metabolites associated with the pathophysiology of several neurological disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stress, anxiety, depression, autism, vascular dementia, schizophrenia, stroke, and neuromyelitis optica spectrum disorders, among others. This review will discuss the current evidence from the most significant studies dealing with some SCFAs from gut microbial metabolism with selected neurological disorders.

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19).

A growing body of evidence indicates that neutrophil elastase (NE) is involved in the pathogenesis of respiratory infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to analyze the dynamic changes in serum levels of NE associated with inflammation, disease activity, and mortality rate in patients with COVID-19. We measured the serum concentrations of NE, C-Reactive protein (CRP), interleukin (IL)- 4, IL-6, IL-8, IL-10, and vitamin D levels in 83 ICU and 69 non-ICU patients compared with 82 healthy subjects (HS) in three-time points (T1-T3). Serum levels of NE, IL-6, IL-8, and CRP in ICU and non-ICU patients were significantly higher than HS (P < 0.001) in three-time points. Also, serum levels of NE, IL-6, IL-8, and CRP in ICU patients were significantly higher than in non-ICU patients (P < 0.05). On the day of admission (T1), the levels of NE, CRP, IL-6, IL-8 were gradually decreased from T1 to T3. At the same time, IL-4 and IL-10 were gradually increased from T1 to T2 and then reduced to T3. Further analyses demonstrated that the levels of NE, IL-6, and IL-8 in deceased patients were significantly higher than in recovered patients (P < 0.05). The ROC curve analysis demonstrated that markers, including NE, IL-6, and IL-8, were valuable indicators in evaluating the activity of COVID-19. Overall, our results signify the critical role of NE in the pathogenesis of COVID-19, and also, further support that NE has a potential therapeutic target for the attenuation of COVID-19 severity.

The role of lovastatin in the attenuation of COVID-19.

The mounting evidence regarding the pathogenesis of COVID-19 indicated that the cytokine storm has an axial role in the severity of this disease, which may lead to thrombotic complications, acute respiratory distress syndrome (ARDS), and myocardial damage, among other consequences. It has recently been demonstrated that statins are known to have anti-viral, anti-inflammatory, anti-thrombotic, and immunomodulatory features; however, their advantage has not been evaluated in COVID-19. This study aimed to investigate the protective effects of lovastatin in intensive care unit (ICU) patients with COVID-19. The case-control study consists of 284 ICU patients, which classified into three groups as follows: 1) the patients who no received lovastatin as a control (92 patients), 2) patients received 20 mg per day lovastatin (99 patients), and 3) patients received 40 mg per day lovastatin (93 patients). Each group's demographic and clinical parameters, along with CRP, interleukin (IL)-6, IL-8 levels, and mortality rate, were studied in three-time points. The results showed that there was no statistically significant difference between our study groups in terms of age and sex. (P > 0.05). Besides, in patients, receiving lovastatin the CRP, IL-6, IL-8 levels were significantly decreased from T1 to T3 than to the control group. Our results also showed that the use of lovastatin in COVID-19 patients significantly reduced the length of hospitalization in the ICU compared with the control group. In addition, our results showed that the mortality rate in patients receiving lovastatin was lower when compared to the control group; however, this difference was not statistically significant. Since the cytokine storm is a significant factor in the pathology of SARS-CoV-2, our findings highlighted the potential use of lovastatin to mitigate the inflammatory response induced by SARS-CoV-2 infection.

A possible pathogenic role of Syndecan-1 in the pathogenesis of coronavirus disease 2019 (COVID-19).

A cell-surface heparan proteoglycan called Syndecan-1 (SDC-1) has multiple roles in healthy and pathogenic conditions, including respiratory viral infection. In this study, we explore the dynamic alternation in the levels of SDC-1 in cases with COVID-19. A total of 120 cases definitely diagnosed with COVID-19 were admitted to the Firoozgar Hospital, Tehran, Iran, from December 1, 2020, to January 29, 2021, and included in our study. Also, 58 healthy subjects (HS) were chosen as the control group. Patients were classified into two groups: 1) ICU patients and (63 cases) 2) non-ICU patients (57 cases). The dynamic changes of serum SCD-1, CRP, IL-6, IL-10, IL-18, and Vit D levels a well as the disease activity were investigated in three-time points (T1-T3). Our results indicated that the COVID-19 patients had significantly increased SCD-1, CRP, IL-6, IL-10, and IL-18 levels than in HS, while the Vit D levels in COVID-19 patients were significantly lower than HS. Further analysis demonstrated that the SCD-1, CRP, IL-6, IL-10, and IL-18 levels in ICU patients were significantly higher than in non-ICU patients. Tracking dynamic changes in the above markers indicated that on the day of admission, the SCD-1, CRP, IL-6, IL-10, and IL-18 levels were gradually increased on day 5 (T2) and then gradually decreased on day 10 (T3). ROC curve analysis suggests that markers mentioned above, SDC-1, IL-6, and IL-18 are valuable indicators in evaluating the activity of COVID-19. All in all, it seems that the serum SDC-1 levels alone or combined with other markers might be a good candidate for disease activity monitoring.

Comparison of Honey versus Polylactide Anti-Adhesion Barrier on Peritoneal Adhesion and Healing of Colon Anastomosis in Rabbits.

BACKGROUND: Postoperative adhesion is still a consequence of intra-abdominal surgeries, which results in bowel obstruction and abdominopelvic pain. Bowel anastomosis as a common abdominal surgery has the incidence of leakage in up to 30% of patients that increase morbidity and mortality. Due to similar pathways of adhesion formation and wound healing, it is important to find a way to reduce adhesions and anastomosis leakage. AIM: This study was designed to compare antiadhesive as well as anastomosis healing improvement effect of honey and polylactide anti-adhesive barrier film. METHODS: Forty-five rabbits divided into three groups of honey, adhesion barrier film, and control group in an animal study. Under a similar condition, rabbits underwent resection and anastomosis of cecum under general anaesthesia. In the first group, honey was used at the anastomosis site, in the second one polylactide adhesion barrier film utilised, and the third one was the control group. Adhesion, as well as anastomosis leakage, was assessed after 21 days. Data were analysed using the Statistical Package for Social Scientists (SPSS) for Windows version 25. RESULTS: Three groups of 15 rabbits were studied. The results showed that mean peritoneal adhesion score (PAS) was lower in the honey group (1.67) in comparison to the adhesion barrier film group (3.40) and the control group (6.33). CONCLUSION: Bio-absorbable polylactide barrier has an anti-adhesion effect but is not suitable for intestinal anastomosis in rabbits. Further studies needed to evaluate these effects on human beings.

The Molecular Detection of Human Bocavirus (HBoV) in Colorectal Tissue with Malignant and Non-Malignant Lesions

Background: Colorectal cancer (CRC) as a worldwide human health concern is identified being a multifactorial subject that infection with specific viral particles such as oncogenic viruses is research interest. Human bocavirus (HBoV) as a recent isolated virus has been investigated in many respiratory and enteric diseases but rare studies evaluates it in tissue specimens especially in cancerous sections. The aim of this study was to detect the presence of HBoV genome and its genotyping in CRC patient's tissue and compare the result with matched healthy control group tissue. Method: in this retrospective case-control study, CRC cases were sporadic and non-familial cancerous while control subjects had healthy or non-malignant lesions in colon tissue. A conventional-PCR performed by specific primers for HBoV VP1 gene. After sequencing of positive PCR products, raw data used for trimming and alignment by bioinformatics software CLC Main Workbench 5 and MEGA5. SPSS v.22 used for statistical calculations. Result: a total of 157 subjects were participated that 66 were diagnosed as CRC cases and 91 were non-CRC colon tissue as control group that matched by the cases. The mean age (y) ± standard deviation of each case and control groups were 59.35±14.48 and 57.21±14.66, respectively. PCR results showed there were 1.3% (2/157) HBoV positive (of each groups one was positive). Sequencing analysis showed all were HBoV-1 genotype. Conclusion: our study showed there are low rate of HBoV genome in Iranian CRC and non-CRC colon tissue. Furthermore, the predominant genotype in our studied subsets were HBoV-1 according to phylogenetic analysis.