Understanding lactate in the development of Hepatitis B virus-related hepatocellular carcinoma.

Hepatitis B Virus (HBV) is a hepatotropic virus that can establish a persistent and chronic infection in humans. Chronic hepatitis B (CHB) infection is associated with an increased risk of hepatic decompensation, cirrhosis, and hepatocellular carcinoma (HCC). Lactate level, as the end product of glycolysis, plays a substantial role in metabolism beyond energy production. Emerging studies indicate that lactate is linked to patient mortality rates, and HBV increases overall glucose consumption and lactate production in hepatocytes. Excessive lactate plays a role in regulating the tumor microenvironment (TME), immune cell function, autophagy, and epigenetic reprogramming. The purpose of this review is to gather and summarize the existing knowledge of the lactate's functions in the dysregulation of the immune system, which can play a crucial role in the development of HBV-related HCC. Therefore, it is reasonable to hypothesize that lactate with intriguing functions can be considered an immunomodulatory metabolite in immunotherapy.

Global investigation of the presence of adenovirus in different types of water resources: a systematic review.

Waterborne viruses such as adenoviruses cause major health problems in the world. Human adenoviruses are the second leading cause of childhood gastroenteritis worldwide. In recent years, the presence of the virus in aquatic resources has been shown in several studies. In this paper, the global presence of adenovirus in different types of water resources are reviewed through studying several surveys conducted in different countries worldwide. We designed one search study to collect the maximum number of related articles to this subject in international databases search engine via relevant keywords. After reviewing the articles, the most relevant ones were selected, and after classification and extracting the required information, they were reported in the tables presented in this study. In general, it was found that the highest rate of the presence of adenoviruses has been reported in sewage water, inlet, and outlet of the treatment plant while the lowest rate of the presence of adenovirus in the dam water. These findings demonstrate that treatment plant system has weakness in removing the adenovirus and are strongly recommended for treatment plants to use new and better protocols to remove this virus. In addition, appropriate diagnostic methods that combines molecular biological technique with infectivity assay should be implemented for detection of adenoviruses in water resources.

NBS superfood: a promising adjunctive therapy in critically ill ICU patients with omicron variant of COVID-19.

This clinical trial aimed to assess the impact of Nutrition Bio-shield superfood (NBS) on clinical status among critically ill ICU patients suffering from acute respiratory distress syndrome (ARDS) due to the Omicron variant of COVID-19. A total of 400 patients with confirmed Omicron-related ARDS were randomly assigned to either the intervention group (n = 200) or the control group (n = 200). Patients in the intervention group received 1.5 g of NBS powder daily for 2 weeks in addition to standard antiviral treatment, while the control group received a placebo alongside standard antiviral therapy. Serum samples were collected from all patients in both groups, and various clinical and laboratory parameters, including ESR, CRP, D-Dimer, CPK, WBC count, lymphocyte count, and lymphocyte percentage, were measured using established methodologies. Following a 14-day intervention period, the intervention group exhibited a significant reduction in mean serum levels of CRP (15.39 vs. 48.49; P < 0.001), ESR (14.28 vs. 34.03; P < 0.001), D-Dimer (485.18 vs. 1009.13; P = 0.001), and CPK (68.93 vs. 131.48; P < 0.001) compared to the control group. Conversely, a significant increase was observed in the mean serum levels of lymphocytes (1537.06 vs. 1152.60; P < 0.001) in the intervention group after 14 days of treatment compared to the control group. The remarkable reduction in inflammatory markers and mortality rates observed with NBS supplementation alongside standard antiviral treatment underscores its crucial role in mitigating inflammation and achieving an important milestone in the fight against COVID-19.

A comprehensive review of highly pathogenic avian influenza (HPAI) H5N1: An imminent threat at doorstep.

Avian influenza viruses (AIVs) are globally challenging due to widespread circulation and high mortality rates. Highly pathogenic avian influenza (HPAI) strains like H5N1 have caused significant outbreaks in birds. Since 2003 to 14 July 2023, the World Health Organization (WHO) has documented 878 cases of HPAI H5N1 infection in humans and 458 (52.16%) fatalities in 23 countries. Recent outbreaks in wild birds, domestic birds, sea lions, minks, and etc., and the occurrence of genetic variations among HPAI H5N1 strains raise concerns about potential transmission and public health risks. This paper aims to provide a comprehensive overview of the current understanding and new insights into HPAI H5N1. It begins with an introduction to the significance of studying this virus and highlighting the need for updated knowledge. The origin and evaluation of HPAI H5N1 are examined, shedding light on its emergence, and spread across different geographic regions. The genome organization and structural biology of the H5N1 virus are explored, providing insights into its molecular composition and key structural features. This manuscript also delves into the phylogeny, evolution, mutational trends, reservoirs, and transmission routes of HPAI H5N1. The immune response against HPAI H5N1 and its implications for vaccine development are analyzed, along with an exploration of the pathogenesis and clinical manifestations of HPAI H5N1 in human cases. Furthermore, diagnostic tools and preventive and therapeutic strategies are discussed, highlighting the current approaches and potential future directions for better management of the potential pandemic.

Design of a multi-epitope-based vaccine consisted of immunodominant epitopes of structural proteins of SARS-CoV-2 using immunoinformatics approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown rapid global spread and has resulted in a significant death toll worldwide. In this study, we aimed to design a multi-epitope vaccine against SARS-CoV-2 based on structural proteins S, M, N, and E. We identified B- and T-cell epitopes and then the antigenicity, toxicity, allergenicity, and similarity of predicted epitopes were analyzed. T-cell epitopes were docked with corresponding HLA alleles. Consequently, the selected T- and B-cell epitopes were included in the final construct. All selected epitopes were connected with different linkers and flagellin and pan-HLA DR binding epitopes (PADRE) as an adjuvant were used in the vaccine construct. Furthermore, molecular docking was used to evaluate the complex between the final vaccine construct and two alleles, HLA-A*02:01 and HLA-DRB1*01:01. Finally, codons were optimized for in silico cloning into pET28a(+) vector using SnapGene. The final vaccine construct comprised 11 CTL, HTL, and B-cell epitopes corresponding to 394 amino acid residues. In silico evaluation showed that the designed vaccine might potentially promote an immune response. Further in vivo preclinical and clinical testing is required to determine the safety and efficacy of the designed vaccine.

Small extracellular vesicles as key players in cancer development caused by human oncogenic viruses.

BACKGROUND: Exosomes are the smallest group of extracellular vesicles in size from 30 to 150 nm, surrounded by a lipid bilayer membrane, and originate from multivesicular bodies secreted by different types of cells, such as virus-infected cells. The critical role of exosomes is information transfer among cells, representing a unique way for intercellular communication via a load of many kinds of molecules, including various signaling proteins and nucleic acids. In this review, we aimed to comprehensively investigate the role of exosomes in promoting human oncogenic viruses-associated cancers. METHODS: Our search was conducted for published researches between 2000 and 2022 by using several international databases includeing Scopus, PubMed, and Web of Science as well as Google scholar. We also reviewed additional evidence from relevant published articles. RESULTS: It has been shown that exosomes can create the conditions for viral spread in viral infections. Exosome secretion in a human tumor virus can switch on the cell signaling pathways by transferring exosome-encapsulated molecules, including viral oncoproteins, signal transduction molecules, and virus-encoded miRNAs, into various cells. CONCLUSION: Given the role of exosomes in viruses-associated cancers, they can also be considered as molecular targets in diagnosis and treatment.

Interplay between cellular metabolism and DNA viruses.

Viruses as intracellular pathogens take over the host metabolism and reprogram to facilitate optimal virus production. DNA viruses can cause alterations in several metabolic pathways, including aerobic glycolysis also known as the Warburg effect, pentose phosphate pathway activation, and amino acid catabolism such as glutaminolysis, nucleotide biosynthesis, lipid metabolism, and amino acid biosynthesis. The available energy for productive infection can be increased in infected cells via modification of different carbon source utilization. This review discusses the metabolic alterations of the DNA viruses that will be the basis for future novel therapeutic approaches.

Frequency of Hepatitis B Markers in Systemic Lupus Erythematosus Patients in Iran.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Hepatitis B virus is the causative agent for chronic, acute, cirrhosis, and hepatocellular carcinoma.  SLE patients with chronic or occult hepatitis B infection undergoing immunosuppressive drugs may become reactive and develop fatal hepatitis. Therefore, this study was conducted to determine HBV markers in SLE patients before the administration of immunosuppressive drugs in Ahvaz city, Iran. MATERIALS AND METHODS: The sera of 92 SLE patients were  tested for HBs Ag and anti-HBc using ELISA, HBV DNA (by Nested PCR) testes. Real-time PCR was performed for the patients with positive anti-HBc and negative HBsAg. The positive HBV DNA samples were checked for HBV genotype and HBV subtypes. RESULTS: Among the 92 SLE patients, three (3.3%) were males and 89 (96.7%) females . The patients' ages ranged from 14 to 70 years [mean age of 38.9±10.1]. Three of 92 (3.26%) subjects [2/3 males and 1/89 female] were positive for HBsAg, anti-HBc Ab, and HBV DNA detected with PCR (p=0.000003)].  Five of 89 (5.61%) subjects [1 male and 4/88 females were only positive for anti-HBc and negative for HBs Ag, HBV DNA(PCR) using Real-time PCR (p=0.05).  The results of the nucleotide data and phylogenetic tree showed all three HBV patients were genotype D1. The results of amino acid sequencing revealed all three HBV patients were HBV subtype ayw2. CONCLUSION: This study proved that 3.26% of SLE patients were positive for overt HBV infection (positive for anti-HBc, HBsAg and HBV-DNA using PCR). All the three isolated HBV were genotype D1 and subtype ayw2. The fact that 5.61% of  the patients were only positive for anti-HBc characterized the occult hepatitis B infection (OBI) although further investigation is needed. To prevent HBV or OBI reactivation for SLE patients before immunosuppression treatment, HBV markers including anti-HBc, HBsAg, HBV-DNA should be implemented using PCR and Real-time PCR .

In silico prediction of T-cell and B-cell epitopes of human papillomavirus type 16 L1 protein.

Human papillomavirus type 16 (HPV-16) is one of the most important cause of developing cervical cancer. Therefore, effective epitope-based vaccine design for HPV-16 would be of major medical benefit. The aim of our study was to identify B- and T-cell epitopes of HPV-16 L1 protein. In this study, the HPV-16 L1 gene was isolated from HPV recovered from five vaginal swab samples using specific primers and finally sequenced. The ExPASy translate tool (http://web.expasy.org/translate/) was used to convert nucleotide sequence into amino acid sequence. Bioinformatic analysis was employed to predict suitable B- and T-cell epitopes and immunogenicity, allergenicity, and toxicity of predicted epitopes were then evaluated. Afterward, the selected T-cell epitopes were docked using Molegro Virtual Docker software. The two epitopes 207 AMDFTTLQA215 and 200 MVDTGFGAM208 have showed a very strong binding affinity to HLA-A0201 and HLA-B3501 molecules, respectively. Outcome of B-cell epitope prediction showed that epitope 475 KAKPKFTLGKRK ATPTTSSTSTTAKRKK502 contained overlapped epitope, which might be the epitope associated with the production of neutralizing antibody response. Based on this finding, the predicted B- and T-cell epitopes are promising targets for epitope-based vaccine development against HPV-16. Further in vivo and in vitro experiments are needed to confirm our findings.

Long noncoding RNAs in respiratory viruses: A review.

Long noncoding RNAs (lncRNAs) are defined as RNA molecules longer than 200 nucleotides that can regulate gene expression at the transcriptional or post-transcriptional levels. Both human lncRNAs and lncRNAs encoded by viruses can modulate the expression of host genes which are critical for viral replication, latency, activation of signalling pathways, cytokine and chemokine production, RNAi processing, expression of interferons (IFNs) and interferon-stimulated genes (ISGs). Studies on lncRNAs as key regulators of host-virus interactions may give new insights into therapeutic strategies for the treatment of related diseases. This current review focuses on the role of lncRNAs, and their interactions with respiratory viruses including influenza A virus (IAV), respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Designing of DNA Vaccine Based on a Secretory Form of Major Capsid Protein of Human Papillomavirus Type 18.

More than 99% of cervical cancers are associated with human papillomaviruses (HPVs) worldwide. Current HPV vaccines are safe, highly immunogenic, with effective immunity against specific HPV types. However, DNA vaccines are a new appealing platform which can be considered for designing the HPV vaccines. This study aimed to construct a recombinant eukaryotic expression plasmid containing L1 of HPV-18, tissue plasminogen activators (tPA), and pan HLA DR-binding epitope (PADRE) genes into the pVAX1 vector. The L1, tPA, and PADRE genes were amplified in a thermocycler. The polymerase chain reaction (PCR) products were cloned and insertion of the genes was confirmed using colony PCR, restriction enzymes analysis, and sequencing methods. Indirect immunofluorescence, RT-PCR, and western blot assays were applied to identify the target gene in HEK-293 cells. Total IgG and its isotypes in immunized mice were measured by enzyme-linked immunosorbent assay technique. Western blot analysis showed a protein band of about 67.5 kDa in supernatant and cell lysate of transfected cells. The results of mice immunization with different constructs (group 1: the pVAX-L1, group 2: pVAX-tPA-PADRE-L1, group 3: pVAX1, and group 4: PBS as controls) indicated that the pVAX1-tPA-PADRE-L1 construct induced a significantly higher level of total IgG than pVAX1-L1 (p=0.003). In conclusion, pVAX1-tPA-PADRE-L1 recombinant plasmid is a highly immunogenic construct and suggests as a promising candidate for vaccine development against HPV type 18 in low-middle-income countries.

Frequency of Hepatitis B Virus infection among Patients before Chemotherapy Treatment.

BACKGROUND: Hepatitis B virus (HBV) is an important public health problem worldwide. Chronic HBV in patients undergoing chemotherapy and immunosuppressive treatment are at risk of HBV reactivation. The consequence of HBV reactivation in immunosuppressed patients may lead to liver failure and death. Therefore, this study was conducted to investigate the frequency of HBV markers in cancer patients before chemotherapy. MATERIALS AND METHODS: In this study cross-sectional, blood samples were collected from 90 cancer patients before chemotherapy. The patient's sera were tested for the presence of HBsAg and anti-HBc using enzyme-linked immunosorbent assay (ELISA). The HBVDNA was tested for patient's sera using nested polymerase chain reaction (nested-PCR). RESULTS: Among 90 patients, 42(46.7%) were males and 48 (53.3%) females, with a mean age of 52.52 ± 11.71 years (range, 25-83 years). Of the 6/90 (6.66%)  patients, including 4/42 (9.5%) males and 2/48 (4.1%) females cases were positive for HBsAg,  anti-HBc and HBV DNA, (P=0.31).  The frequency of HBV infection in cancer patients  was rectal 3(3.33%),  breast cancer  2 (2.22%) and prostate 1(1.11%) cases. The sera of 8/84 (9.52%) patients including 5/39 (12.82%) males and 3/45 (6.66%) females tested positive for anti-HBc, but negative for HBsAg and HBV DNA. (P=0.55). The results of phylogenetic tree revealed that  four isolated HBV DNA in cancer patients were cluster with genotype D. CONCLUSIONS: High frequency of 6.66%  HBV infection have been observed in cancer patients before chemotherapy. The sera of  9.52% patients were only positive for anti-HBc IgG which may indicate the past HBV infection or presence of OBI but requires further investigation. To prevent HBV or OBI reactivation, the screening of HBV DNA and anti HBc should be implemented for cancers patients before chemotherapy.

Interactions between SARS coronavirus 2 papain-like protease and immune system: A potential drug target for the treatment of COVID-19.

Coronaviruses (CoVs) are a large family of respiratory viruses which can cause mild to moderate upper respiratory tract infections. Recently, new coronavirus named as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified which is a major threat to public health. Innate immune responses play a vital role in a host's defence against viruses. Interestingly, CoVs have evolved elaborate strategies to evade the complex system of sensors and signalling molecules to suppress host immunity. SARS-CoV-2 papain-like protease (PLpro), as an important coronavirus enzyme, regulates viral spread and innate immune responses. SCoV-2 PLpro is multifunctional enzyme with deubiquitinating (DUB) and deISGylating activity. The PLpro can interact with key regulators in signalling pathways such as STING, NF-κB, cytokine production, MAPK and TGF-ß and hijack those to block the immune responses. Therefore, the PLpro can be as an important target for the treatment of COVID-19. Until now, several drugs or compounds have been identified that can inhibit PLpro activity. Here we discuss about the dysregulation effects of PLpro on immune system and drugs that have potential inhibitors for SCoV-2 PLpro.

Seronegative occult hepatitis C infection among hemodialysis patients: A prevalence study.

The aim of this study was to investigate the prevalence of occult hepatitis C virus (HCV) infection (OCI) among HD patients. Blood samples were taken from 79 HD patients and their sera were evaluated for the presence of anti-HCV. Both the sera and peripheral blood mononuclear cells (PBMCs) were then checked for HCV RNA by nested reverse transcriptase-polymerase chain reaction. Anti-HCV was positive among 4/79 (5.1%) of the patients. From 75 patients who were negative for anti-HCV, 71 (94.7%) patients were also negative for HCV RNA in sera samples but five of them were positive for HCV RNA in PBMCs. Totally, out of 79 patients, HCV RNA was detected in PBMCs of five (6.3%) patients, indicating that these patients had OCI. No significant difference was observed between the frequency of OCI and gender (P-value = .6). HCV genotype in all five cases of OCI was genotype 3a. Our study showed prevalence rate of 6.3% OCI infection in HD patients. Regarding the serious complications and the clinical importance of OCI in HD patients, sensitive diagnostic methods for identifying HCV RNA in the PBMCs should be implemented for all HD patients.

Dominance of Variant Human Herpesvirus 6 A Among Hemodialysis Patients, Ahvaz, Iran.

INTRODUCTION: Hemodialysis (HD) patients are a high-risk population for acquiring blood-borne viruses such as HHV-6. HHV-6 can remain latent in the host cells after primary infection; the reactivation of virus may result complications such as seizure, respiratory failure, hepatitis, and encephalitis. There is a limited report concerning HHV-6 infection in HD patients in Iran. Thus, this study was conducted to determine the frequency of HHV-6 among HD patients. METHODS: We determined HHV-6 DNA in sera samples of 84 patients undergoing HD. The DNA was extracted from the sera samples and the presence of HHV-6 DNA variants A and B was evaluated by nested PCR. RESULTS: 52/84 (61.9%) of HD patients were males and 32/84 (38.1%) females. The age ranges of patients were between 18 to 85 years and the mean age was 52 ± 1.52 (± SD) years. Out of 84 sera samples, HHV-6 DNA was detected in 10 (11.9%) participants, including 6/52 (11.5%) in males and 4/32 (12.5%) in females. HHV- 6A was detected in 10/10 (100%) of positive cases. No HHV-6 B was found in HD patients. The distribution of HHV-6A DNA was not significant between genders (P > .05). Out of 84 HD patients, 55 (65.47%) cases were over 50 years, among them 10 (18.18%) cases were positive for HHV-6 A infection (P < .05). CONCLUSION: The results showed that only HHV-6 DNA variant A was found in 11.9% of HD patients. Regarding the consequence of HHV-6 reactivation, to manage and improve treatment, the screening of HHV-6 DNA test should be implemented for HD patients.

The frequency of Epstein-Barr virus among hemodialysis patients, Ahvaz, Iran.

BACKGROUND AND OBJECTIVES: Epstein-Barr virus (EBV) has infected more than 90% of adults worldwide. EBV infection is asymptomatic in healthy individuals and is controlled by a robust immune response while in individuals with weakened immunesystems including Hemodialysis (HD) patients and transplant recipients leads to serious illnesses. This study was aimed to investigate the frequency of EBV among the HD patients. MATERIALS AND METHODS: The cross-sectional study was carried out on 84 HD patients. These sera were checked for anti-EBV (VCA) IgG Ab assessment using enzyme-linked immunosorbent assay (ELISA). The DNA was extracted from the sera samples and tested for EBV DNA using nested PCR. RESULTS: 52/84 (61.9%) of HD were males and 32/84 (38.1%) were females. The average age of participants was varying from 18 to 85 years while the mean age was 52 ± 1.57 SD years. 81 of 84 (96.42%); including 49/52 (94.23%) male and 32/32 (100%) female, were positive for anti-EBV (VCA) IgG antibody while 3 (3.58%) were negative. No significant differences were observed between the subjects regarding gender (P=0.28). EBV DNA was detected in 7 (8.33%) individuals, including 6 (11.53%) and 1 (3.12%) in male and female, respectively (P=0.24). CONCLUSION: Our study results showed that high prevalence of anti-EBV (VCA) IgG antibody (96.42%) were observed among the HD patients. Although the status of EBV latency was not performed, but it seems many of these patients are at risk of EBV-reactivation during the organ transplantation. As a result, it is recommended that the detection of EBNA-1 gene as a marker of EBV latency should be implemented for all HD patients to prevent EBV reactivation during organ transplantation.

Complexity on modulation of NF-κB pathways by hepatitis B and C: A double-edged sword in hepatocarcinogenesis.

Nuclear factor-κB (NF-κB), a family of master regulated dimeric transcription factors, signaling transduction pathways are active players in the cell signaling that control vital cellular processes, including cell growth, proliferation, differentiation, apoptosis, morphogenesis, angiogenesis, and immune responses. Nevertheless, aberrant regulation of the NF-κB signaling pathways has been associated with a significant number of human cancers. In fact, NF-κB acts as a double-edged sword in the vital cellular processes and carcinogenesis. This review provides an overview on the modulation of the NF-κB signaling pathways by proteins of hepatitis B and C viruses. One of the major NF-κB events that are modulated by these viruses is the induction of hepatocellular carcinoma. Given the central function of NF-κB in carcinogenesis, it has turned out to be a considerable therapeutic target for cancer therapy.

Hepatitis C virus core protein modulates several signaling pathways involved in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer, and hepatitis C virus (HCV) infection plays a major role in HCC development. The molecular mechanisms by which HCV infection leads to HCC are varied. HCV core protein is an important risk factor in HCV-associated liver pathogenesis and can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of signaling pathways such as transforming growth factor ß (TGF-ß), vascular endothelial growth factor (VEGF), Wnt/ß-catenin (WNT), cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor α (PPARα) by HCV core protein is implicated in the development of HCC. Therefore, it has been suggested that this protein be considered a favorable target for further studies in the development of HCC. In addition, considering the axial role of these signaling pathways in HCC, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HCV-related HCC.