Cancer therapy with the viral and bacterial pathogens: The past enemies can be considered the present allies.

Cancer continues to be one of the leading causes of mortality worldwide despite significant advancements in cancer treatment. Many difficulties have arisen as a result of the detrimental consequences of chemotherapy and radiotherapy as a common cancer therapy, such as drug inability to penetrate deep tumor tissue, and also the drug resistance in tumor cells continues to be a major concern. These obstacles have increased the need for the development of new techniques that are more selective and effective against cancer cells. Bacterial-based therapies and the use of oncolytic viruses can suppress cancer in comparison to other cancer medications. The tumor microenvironment is susceptible to bacterial accumulation and proliferation, which can trigger immune responses against the tumor. Oncolytic viruses (OVs) have also gained considerable attention in recent years because of their potential capability to selectively target and induce apoptosis in cancer cells. This review aims to provide a comprehensive summary of the latest literature on the role of bacteria and viruses in cancer treatment, discusses the limitations and challenges, outlines various strategies, summarizes recent preclinical and clinical trials, and emphasizes the importance of optimizing current strategies for better clinical outcomes.

Role of lncRNAs in Helicobacter pylori and Epstein-Barr virus associated gastric cancers.

Helicobacter pylori infection is a risk factor for the development of gastric cancer (GC), and the role of co-infection with viruses, such as Epstein-Barr virus, in carcinogenesis cannot be ignored. Furthermore, it is now known that genetic factors such as long non-coding RNAs (lncRNAs) are involved in many diseases, including GC. On the other side, they can also be used as therapeutic goals. Modified lncRNAs can cause aberrant expression of genes encoding proximal proteins, which are essential for the development of carcinoma. In this review, we present the most recent studies on lncRNAs in GC, concentrating on their roles in H. pylori and EBV infections, and discuss some of the molecular mechanisms of these GC-related pathogens. There was also a discussion of the research gaps and future perspectives.

Therapeutic potential of phospho-thiadiazole derivatives as anti-glioblastoma agents: synthesis, biological assessment and computational study.

In this study, three new phospho thiadiazole compounds (A, F and W) were investigated as possible cytotoxic agents. The compounds were synthesised and characterised by using spectroscopy methods. The crystal structure of compound A was investigated using X-ray crystallography, since the title compounds can exist as different tautomeric forms, their conformational and geometrical aspects were investigated computationally by the DFT method. NBO analysis suggested that these compounds can function as appropriate ligands for the reaction with the nitrogen bases of DNA. All the synthesised compounds were evaluated in vitro for their cytotoxic activities against cancer in the human glioblastoma cell lines (U-251) using the MTT assay. According to the annexin V-FITC/PI results, a combination of synthesised compounds with ReoT3D showed a synergistic effect to increase the percentage of apoptotic cells. Molecular docking study for A (the most toxic compound) showed how it interacts with DNA. Both in vitro and in silico results showed that A has promising inhibitory potential (IC50: 48.1 ± 0.3 µM) and binding energy (-6.67 kcal/mol).

Recent Advances in Early Diagnosis of Viruses Associated with Gastroenteritis by Biosensors.

Gastroenteritis, as one of the main worldwide health challenges, especially in children, leads to 3-6 million deaths annually and causes nearly 20% of the total deaths of children aged ˂5 years, of which ~1.5 million gastroenteritis deaths occur in developing nations. Viruses are the main causative agent (~70%) of gastroenteritis episodes and their specific and early diagnosis via laboratory assays is very helpful for having successful antiviral therapy and reduction in infection burden. Regarding this importance, the present literature is the first review of updated improvements in the employing of different types of biosensors such as electrochemical, optical, and piezoelectric for sensitive, simple, cheap, rapid, and specific diagnosis of human gastroenteritis viruses. The Introduction section is a general discussion about the importance of viral gastroenteritis, types of viruses that cause gastroenteritis, and reasons for the combination of conventional diagnostic tests with biosensors for fast detection of viruses associated with gastroenteritis. Following the current laboratory detection tests for human gastroenteritis viruses and their limitations (with subsections: Electron Microscope (EM), Cell Culture, Immunoassay, and Molecular Techniques), structural features and significant aspects of various biosensing methods are discussed in the Biosensor section. In the next sections, basic information on viruses causing gastroenteritis and recent developments for fabrication and testing of different biosensors for each virus detection are covered, and the prospect of future developments in designing different biosensing platforms for gastroenteritis virus detection is discussed in the Conclusion and Future Directions section as well.

Genosensors as an alternative diagnostic sensing approaches for specific detection of virus species: A review of common techniques and outcomes.

Viral infections are responsible for the deaths of millions of people throughout the world. Since outbreak of highly contagious and mutant viruses such as contemporary sars-cov-2 pandemic, has challenged the conventional diagnostic methods, the entity of a thoroughly sensitive, specific, rapid and inexpensive detecting technique with minimum level of false-positivity or -negativity, is desperately needed more than any time in the past decades. Biosensors as minimized devices could detect viruses in simple formats. So far, various nucleic acid, immune- and protein-based biosensors were designed and tested for recognizing the genome, antigen, or protein level of viruses, respectively; however, nucleic acid-based sensing techniques, which is the foundation of constructing genosensors, are preferred not only because of their ultra-sensitivity and applicability in the early stages of infections but also for their ability to differentiate various strains of the same virus. To date, the review articles related to genosensors are just confined to particular pathogenic diseases; In this regard, the present review covers comprehensive information of the research progress of the electrochemical, optical, and surface plasmon resonance (SPR) genosensors that applied for human viruses' diseases detection and also provides a well description of viruses' clinical importance, the conventional diagnosis approaches of viruses and their disadvantages. This review would address the limitations in the current developments as well as the future challenges involved in the successful construction of sensing approaches with the functionalized nanomaterials and also allow exploring into core-research works regarding this area.

Understanding the pivotal roles of ACE2 in SARS-CoV-2 infection: from structure/function to therapeutic implication.

In December 2019, a novel respiratory tract infection, from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in China that rapidly spread around the world. This virus possesses spike (S) glycoproteins on the surface of mature virions, like other members of coronaviridae. The S glycoprotein is a crucial viral protein for binding, fusion, and entry into the target cells. Binding the receptor-binding domain (RBD) of S protein to angiotensin-converting enzyme 2 (ACE 2), a cell-surface receptor, mediates virus entry into cells; thus, understanding the basics of ACE2 and S protein, their interactions, and ACE2 targeting could be a potent priority for inhibition of virus infection. This review presents current knowledge of the SARS-CoV-2 basics and entry mechanism, structure and organ distribution of ACE2, and also its function in SARS-CoV-2 entry and pathogenesis. Furthermore, it highlights ACE2 targeting by recombinant ACE2 (rACE2), ACE2 activators, ACE inhibitor, and angiotensin II (Ang II) receptor blocker to control the SARS-CoV-2 infection.

Relative frequency of hepatitis B virus, human papilloma virus, Epstein-Barr virus, and herpes simplex viruses in the semen of fertile and infertile men in Shiraz, Iran: A cross-sectional study.

BACKGROUND: About 8-12% of couples on reproductive age suffers from infertility worldwide. Since 1993, the role of genital tract infections by microbes, including viruses that can infect the sperm, in human infertility has been proposed. OBJECTIVE: To investigate the frequency of hepatitis B virus (HBV), human papilloma virus (HPV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV) infection in the semen of fertile and infertile men referred to the Mother and Child Hospital, Shiraz, Iran. MATERIALS AND METHODS: In this cross-sectional study, 350 men including 200 infertile and 150 fertile men were included. All semen samples were allowed to liquefy, followed by the assessment of sperm parameters. DNA was extracted using a DNA extraction kit (CinaGene, Tehran, Iran) according to the manufacturer's instructions. Detection of HBV, HPV, EBV, and HSV1/2 was done by the PCR method. RESULTS: The mean age of the participants was 36 ± 7 yr. Molecular results showed that 16 samples (8%) of infertile men and 5 (3.3%) of fertile men were positive for HBV, which was not statistically significant (p = 0.069). Only one sample of the fertile participants was positive for HPV. None of the semen samples of the infertile or fertile groups was positive for the presence of EBV or HSV1/2. CONCLUSION: The results of this study indicated that HBV, HPV, EBV, and HSV might not be involved in men's infertility. Further studies are recommended for clarifying the role of these viruses in infertility.

Prevalence and clinical manifestations of herpes simplex virus infection among suspected patients of herpes simplex encephalitis in Shiraz, Iran.

Encephalitis has infectious and noninfectious etiology. Among infectious agents, viruses are the main causes of encephalitis; Herpes simplex virus (HSV) is known as the most common causative agent of viral encephalitis. In this current cross-sectional investigation, we aimed to assess the prevalence of HSV in the cerebrospinal fluid (CSF) specimens of Herpes Simplex Encephalitis (HSE) suspected patients and also determining the clinical symptoms and laboratory findings of this viral complication. Two hundred consecutive HSE suspected patients with clinical diagnosis of encephalitis were included in the study and then the presence of HSV DNA in their CSF was applied by Polymerase Chain Reaction (PCR) assay. Molecular detection of two hundred (117 males with mean age: 43 years, 83 females with mean age: 39 years) CSF samples showed that 22 (11.11%) cases were positive for HSV infection. 15(68.18%) of the positive samples were more than 50 years old, however, there was no significant correlation between age distribution, gender and HSE clinical manifestations. Fever (91%), headache (72.7%), seizer (59%), and weakness (59%) were the most common symptoms in positive patients and also mortality rate was (18.18%). CSF laboratory abnormalities of HSE cases were as follows; lymphocytic pleocytosis 19 (86.3%), leukocytosis 19 (86.3%), elevated protein level 16 (72.7%), and hypoglycorrhachia 3(13.6%). Screening of HSE suspected patients is crucial in the treatment of patients and reduce the mobility and morbidity of patients. Qualitative PCR as an available method in most developing countries could be a reliable method to monitor consecutive HSE suspected patients.

Mesenchymal stem cells loaded with oncolytic reovirus enhances antitumor activity in mice models of colorectal cancer.

Oncolytic viruses (OVs) are promising alternative biological agents for treating cancer. However, triggered immune responses against viruses and their delivery to tumor sites are their primary limitations in cancer therapy. To address these challenges, mesenchymal stem cells (MSCs) can serve as permissive tools for OVs loading and delivery to tumor sites. Here, we evaluated the in vitro and in vivo antitumor capability of adipose-derived mesenchymal stem cells (AD-MSCs) as a new vehicle for Dearing strain of reovirus (ReoT3D) loading. We first isolated and confirmed the purity of MSCs, and the optimized dose of ReoT3D for MSCs loading was computed by a standard assay. Next, we used murine CT26 cell line to establish the colorectal cancer model in BALB/c mice and demonstrated the antitumor effects of MSCs loaded with reovirus. Our results demonstrated that multiplicity of infection (MOI) 1 pfu/cells of reovirus was the safe dose for loading into purified MSCs. Moreover, our anticancer experiments exhibited that treatment with MSCs loaded with ReoT3D was more effective than ReoT3D and MSCs alone. Higher anticancer impact of MSCs loaded with OV was associated with induction of apoptosis, cell cycle arrests, P53 expression in tumor sections, and reduced tumor growth and size. The present results suggest that MSCs as a permissive shuttle for oncolytic virus (OV) delivery increased the anticancer activity of ReoT3D in mice models of colorectal cancer and these findings should be supported by more preclinical and clinical studies.

Gold nanoparticles show potential in vitro antiviral and anticancer activity.

AIMS: Gold nanoparticles (AuNPs) have been attracted interests in the various areas of clinical therapeutics. In this study, we investigated the anticancer and antiviral potential activity of AuNPs against influenza A virus and human glioblastoma (GMB) U-87 and U-251 cell lines. MAIN METHODS: Gold nanoparticles (AuNPs) were synthesized by citrate reduction method. Then, ultraviolet-visible spectrophotometry (UV-vis spectra) and electron microscopy analysis confirmed the type, size (mean diameter of 17 nm) and distribution of the particles. The AuNPs in vitro antiviral and anticancer effects was evaluated by hemagglutination inhibition (HAI), tissue culture infectious dose 50 (TCID50), real-time PCR, MTT, flow cytometry, and scratch assays. KEY FINDINGS: The AuNPs were synthesized in spherical with a mean diameter of 17 ± 2 nm and an absorbance peak at 520 nm. The AuNPs were well tolerable by MDCK cells at concentrations up to 0.5µg/ml and they significantly inhibited the hemagglutination and virus infectivity, particularly when added pre- or during virus infection. Furthermore, anticancer results indicated that AuNPs treatment caused the marked induction of apoptosis and reduced growth and migration capability of U-87 and U-251 cell lines in a time-dependent manner. SIGNIFICANCE: The present results suggest that AuNPs provide promising antiviral and anticancer approaches. Further research is needed to fully elucidate the mode of antiviral and anticancer action of AuNPs against influenza virus infection and human glioblastoma cell lines.

In Vitro Anti-cancer Activity of Adipose-Derived Mesenchymal Stem Cells Increased after Infection with Oncolytic Reovirus.

Purpose: Reovirus type 3 Dearing (ReoT3D), a wild type oncolytic virus (OV) from the Reoviridae family, kills KRAS mutant cancer cells. However, the use of OVs has faced with some limitations such as immune responses, and delivery of OVs to the tumor sites in systemic therapy. To solve this, and also to increase the anti-cancer effects of these OVs, mesenchymal stem cells (MSCs) might be used as an effective vehicle for OVs delivery. In this study, we examined the anti-cancer effects of human adipose derived-MSCs (AD-MSCs) as a vehicle of ReoT3D against human glioblastoma cells. Methods: Here, AD-MSCs were characterized and toxicity of ReoT3D on them was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Then, capability of AD-MSCs for virus production was assessed by real-time polymerase chain reaction (PCR), and different in vitro anti-cancer experiments were applied for our anti-cancer purposes. Results: Our results from toxicity assay revealed that the isolated and provoked AD-MSCs were resistant to nontoxic concentration multiplicity of infection (MOI) >1 pfu/cells of ReoT3D. In addition, the results indicated that AD-MSCs were susceptible for virus life cycle complementation and were capable for production of virus progenies. Furthermore, our results showed that AD-MSCs had oncolysis effects and increased the anti-cancer effects of ReoT3D. Conclusion: AD-MSCs as a susceptible host for oncolytic reovirus could increase the anti-cancer activity of this OV against glioblastoma multiforme (GBM) cell line.

The role of Th17 cells in viral infections.

The present review provides an overview of recent advances regarding the function of Th17 cells and their produced cytokines in the progression of viral diseases. Viral infections alone do not lead to virus-induced malignancies, as both genetic and host safety factors are also involved in the occurrence of malignancies. Acquired immune responses, through the differentiation of Th17 cells, form the novel components of the Th17 cell pathway when reacting with viral infections all the way from the beginning to its final stages. As a result, instead of inducing the right immune responses, these events lead to the suppression of the immune system. In fact, the responses from Th17 cells during persistent viral infections causes chronic inflammation through the production of IL-17 and other cytokines which provide a favorable environment for tumor growth and its development. Additionally, during the past decade, these cells have been understood to be involved in tumor progression and metastasis. However, further research is required to understand Th17 cells' immune mechanisms in the vast variety of viral diseases. This review aims to determine the roles and effects of the immune system, especially Th17 cells, in the progression of viral diseases; which can be highly beneficial for the diagnosis and treatment of these infections.

Involvement of EGFR, ERK-1,2 and AKT-1,2 Activity on Human Glioma Cell Growth.

GBM (Glioblastoma multiforme) is the  most prevalent and lethal primary brain tumor. Gene therapy is one of the promising approaches and  involves the delivery of genetic therapeutic molecules for specific antitumour response/activity. miRNAs can regulate the cell biology functions including replication, cell growth, and apoptosis by regulating gene expression. In this study, we found that down-regulation of miR-4731 expression occurred in GBM cells. We further determined that miR-4731 behaved as a tumor suppressor by inhibiting GBM cell proliferation. We further investigated the molecular mechanisms of miR-4731 and EGFR, ERK-1,2 and AKT-1,2 in GBM cell lines U87 and U251. The in vitro ectopic expression of miR-4731 affected cell proliferation, migration, and invasion of U87 and U251 cells. Luciferase reporter assays validated that miR-4731 targeted the 3'-untranslated region (3'-UTR) of EGFR. In conclusions, we identified that miR-4731 plays a tumor suppressor role in GBM cell proliferation and migration by targeting EGFR expression, and miR-4731 may act as a novel biomarker for early diagnosis or therapeutic target of GBM.

The synergistic anticancer effects of ReoT3D, CPT-11, and BBI608 on murine colorectal cancer cells.

BACKGROUND: Many types of oncolytic viruses (OVs) were enrolled in clinical trials. Recently, an OV named Talimogene laherparepvec approved for the treatment of melanoma. This achievement highlighted the clinical application of OVs. Scientists focus on using these anticancer agents in combination with the current or/and new anticancer chemotherapeutics. They aim to increase the oncolytic effect of a new approach for the treatment of cancer cells. OBJECTIVES: The present study aimed to assess the anticancer impacts of ReoT3D, irinotecan (CPT-11), and napabucasin (BBI608) against murine colorectal cancer cells (CT26). They are assessed alone and in combination with each other. METHODS: Here, oncolytic reovirus was propagated and titrated. Then MTT assay was carried out to assess the toxicity of this OV and chemotherapeutics effect on CT26 cells. The anticancer effects of ReoT3D, CPT-11, and BBI608, alone and simultaneously, on CT26 cell line, were assessed by the induction of apoptosis, cell cycle arrest, colony-forming, migration, and real-time PCR experiments. RESULTS: Alone treatment with ReoT3D, CPT-11, and BBI608 led to effectively inducing of apoptosis, cell cycle arrest, and apoptotic genes expression level and significantly reduce of colony-forming, migration, and anti-apoptotic genes expression rate. Importantly, the maximum anticancer effect against CT26 cell line was seen upon combination ReoT3D, CPT-11, and BBI608 treatment. CONCLUSION: The present study highlights that combination of ReoT3D, CPT-11, and BBI560 showed synergistic anticancer activity against CT26 cell line. This modality might be considered as a new approach against colorectal cancer (CRC) in the in vivo and clinical trial investigations.