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Abstract: Epidemiological evidence continues to accumulate on the effect of stress and depression on cancer initiation and progression. Depression has been introduced as an independent predictor of increased cancer mortality. At the same time, early intervention for depression increases the surviv-al rate. Even some evidence has given prognostic value for depression to predict cancer recurrence and mortality. This article presents current evidence on the correlations of molecular mechanisms of cancer and depression through; I. The evidence shows the role of pre-existing depression and anxie-ty in the development and progression of cancer. II. The Immune system performs a crucial role in stress, depression, and cancer. III. The role of stress and depression-induced inflammation. IV. The evidence has proposed that cancer may result in depression and the effect of depression on cancer outcomes. In conclusion, the importance of preventive interventions to monitor patients’ mental health during cancer treatment is very significant and should not be underestimated. In other words, the initial interventions can improve depressive symptoms and increase cancer survival. On the oth-er hand, by identifying key biomarkers of depression, physicians can identify cancer patients at risk for depression or those who may not respond to routine treatments. Revealing the molecular mecha-nism of the cancer microenvironment in the development of comorbidities promises innovative therapeutic options for cancer. Identifying these mechanisms opens a new avenue in identifying cancer patients at risk for depression and can also provide considerable potential in identifying de-pressive patients prone to cancer.

Abstract: Despite repeated attempts to discover and develop novel effective therapeutic platforms, major hurdles remain to treat gastrointestinal cancers. The discovery of novel biomarkers is an important step in cancer treatment. MiRNAs have appeared as potent prognostic, diagnostic, and therapeutic biomarkers for a variety of cancers, including gastrointestinal cancers. They are quick, easy to detect, noninvasive, and inexpensive. MiR-28 is associated with a variety of gastrointestinal cancers, including esophageal, gastric, pancreatic, liver, and colorectal cancer. MiRNA expression is deregulated in cancer cells. Hence, the miRNAs expression patterns can be used to detect the subgroups of patients, the result is getting early detection and efficient treatment. miRNAs have an oncogenic or tumor-suppressor role based on tumor tissue, and cell types. It has been shown that dysregulation of miR-28 is involved in GI cancer occurrence, cancer cell growth and metastasis. Due to the limitations of single research and the lack of consensus results, in this review, we aim to summarize the current research advances in the diagnostic, prognostic, and therapeutic potential of circulating miR-28 levels in human gastrointestinal cancers.

MicroRNAs (miRNAs) are highly conserved non-coding RNAs involved in many physiological processes such as cell proliferation, inhibition, development of apoptosis, differentiation, suppression of tumorigenicity, and regulation of cell growth. The description of the alterations of miRNA expression patterns in cancers will be helpful in recognizing biomarkers for early detection and possible therapeutic intervention in the treatment of cancers. Recent studies have shown that miR-451 is broadly dysregulated in lung cancer and is a crucial agent in lung tumor progression. This review summarizes recent advances in the potential role of miR-451 in lung cancer diagnosis, prognosis, and treatment and provides an insight into the potential use of miR-451 for the development of advanced therapeutic methods in lung cancer.

Background Colorectal cancer which is related to genetic and environmental risk factors, is among the most prevalent life-threatening cancers. Although several pathogenic bacteria are associated with colorectal cancer etiology, some others are considered as highly selective therapeutic agents in colorectal cancer. Nowadays, researchers are concentrating on bacteriotherapy as a novel effective therapeutic method with fewer or no side effects to pay the way of cancer therapy. The introduction of advanced and successful strategies in bacterial colorectal cancer therapy could be useful to identify new promising treatment strategies for colorectal cancer patients. Main text In this article, we scrutinized the beneficial effects of bacterial therapy in colorectal cancer amelioration focusing on different strategies to use a complete bacterial cell or bacterial-related biotherapeutics including toxins, bacteriocins, and other bacterial peptides and proteins. In addition, the utilization of bacteria as carriers for gene delivery or other known active ingredients in colorectal cancer therapy are reviewed and ultimately, the molecular mechanisms targeted by the bacterial treatment in the colorectal cancer tumors are detailed. Conclusions Application of the bacterial instrument in cancer treatment is on its way through becoming a promising method of colorectal cancer targeted therapy with numerous successful studies and may someday be a practical strategy for cancer treatment, particularly colorectal cancer.

Despite the improvements in endovascular techniques during the last decades, there is still an increase in the prevalence of peripheral artery disease (PAD) with limited practical treatment, which timeline impact of any intervention for critical limb ischemia (CLI) is poor. Most common treatments are not suitable for many patients due to their underlying diseases, including aging and diabetes. On the one hand, there are limitations for current therapies due to the contraindications of some individuals, and on the other hand, there are many side effects caused by common medications, for instance, anticoagulants. Therefore, novel treatment strategies like regenerative medicine, cell-based therapies, Nano-therapy, gene therapy, and targeted therapy, besides other traditional drugs combination therapy for PAD, are newly considered promising therapy. Genetic material encoding for specific proteins concludes with a potential future for developed treatments. Novel approaches for therapeutic angiogenesis directly used the angiogenetic factors originating from key biomolecules such as genes, proteins, or cell-based therapy to induce blood vessel formation in adult tissues to initiate the recovery process in the ischemic limb. As PAD is associated with high mortality and morbidity of patients causing disability, considering the limited treatment choices for these patients, developing new treatment strategies to prevent PAD progression and extending life expectancy, and preventing threatening complications is urgently needed. This review aims to introduce the current and the novel strategies for PAD treatment that lead to new challenges for relief the patient's suffered from the disorder.

Epidemiological evidence continues to accumulate on the effect of stress and depression with cancer initiation and progression. Depression has been introduced as an independent predictor of increased cancer mortality. Whereas early intervention for depression increases the survival rate. Even some evidence has given prognostic value for depression to predict cancer recurrence and mortality. This article presents current evidence on the correlations of molecular mechanisms of cancer and depression through; I. The evidence shows the role of pre-existing depression and anxiety in the development and progression of cancer. II. The Immune system performs a crucial role in stress, depression, and cancer. III. The role of stress and depression-induced inflammation. IV. The evidence has proposed that cancer may result in depression and the effect of depression on cancer outcome. In conclusion, the importance of preventive interventions to monitor patients' mental health during cancer treatment is very significant and should not be underestimated. In other words, the initial interventions can improve depressive symptoms and increase cancer survival. On the other hand, by identifying key biomarkers of depression, physicians can identify cancer patients who are at risk for depression or those who may not respond to routine treatments. Understanding how the cancer environment can cause pathophysiological phenomena helps develop new anti-depressant therapies and identify cancer patients that may be present during cancer. It can also help if the patients with cancer are prone to depression.

Pancreatic cancer (PC) is a lethal malignancy cancer, and its mortality rates have been increasing worldwide. Diagnosis of this cancer is complicated, as it does not often present symptoms, and most patients present an irremediable tumor having a 5-year survival rate after diagnosis. Regarding treatment, many concerns have also been raised, as most tumors are found at advanced stages. At present, anticancer compounds-rich foods have been utilized to control PC. Among such bioactive molecules, flavonoid compounds have shown excellent anticancer abilities, such as quercetin, which has been used as an adjunctive or alternative drug to PC treatment by inhibitory or stimulatory biological mechanisms including autophagy, apoptosis, cell growth reduction or inhibition, EMT, oxidative stress, and enhancing sensitivity to chemotherapy agents. The recognition that this natural product has beneficial effects on cancer treatment has boosted the researchers’ interest towards more extensive studies to use herbal medicine for anticancer purposes. In addition, due to the expensive cost and high rate of side effects of anticancer drugs, attempts have been made to use quercetin but also other flavonoids for preventing and treating PC. Based on related studies, it has been found that the quercetin compound has significant effect on cancerous cell lines as well as animal models. Therefore, it can be used as a supplementary drug to treat a variety of cancers, particularly pancreatic cancer. This review is aimed at discussing the therapeutic effects of quercetin by targeting the molecular signaling pathway and identifying antigrowth, cell proliferation, antioxidative stress, EMT, induction of apoptotic, and autophagic features.

Lymphoma is a name for malignant diseases of the lymphatic system including Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Although several approaches are used for the treatment of these diseases, some of them are not successful and have serious adverse effects. Therefore, other effective treatment methods might be interesting. Studies have indicated that plant ingredients play a key role in treating several diseases. Some plants have already shown a potential therapeutic effect on many malignant diseases. Quercetin is a flavonoid found in different plants and could be useful in the treatment of different malignant diseases. Quercetin has its antimalignant effects through targeting main survival pathways activated in tumor cells. In vitro/in vivo experimental studies have demonstrated that quercetin possesses a cytotoxic effect on lymphoid cancer cells. Regardless of the optimum results that have been obtained from both in vitro/in vivo studies, few clinical studies have analyzed the antitumor effects of quercetin in lymphoid cancers. Thus, it seems that more clinical studies should introduce quercetin as a therapeutic, alone or in combination with other chemotherapy agents. Here, in this study, we reviewed the anticancer effects of quercetin and highlighted the potential therapeutic effects of quercetin in various types of lymphoma.

Summary The novel coronavirus (SARS‐CoV‐2) has turned into a life‐threatening pandemic disease (Covid‐19). About 5% of patients with Covid‐19 have severe symptoms including septic shock, acute respiratory distress syndrome, and the failure of several organs, while most of them have mild symptoms. Frequently, the kidneys are involved through direct or indirect mechanisms. Kidney involvement mainly manifests itself as proteinuria and acute kidney injury (AKI). The SARS‐CoV‐2‐induced kidney damage is expected to be multifactorial; directly it can infect the kidney podocytes and proximal tubular cells and based on an angiotensin‐converting enzyme 2 (ACE2) pathway it can lead to acute tubular necrosis, protein leakage in Bowman's capsule, collapsing glomerulopathy and mitochondrial impairment. The SARS‐CoV‐2‐driven dysregulation of the immune responses including cytokine storm, macrophage activation syndrome, and lymphopenia can be other causes of the AKI. Organ interactions, endothelial dysfunction, hypercoagulability, rhabdomyolysis, and sepsis are other potential mechanisms of AKI. Moreover, lower oxygen delivery to kidney may cause an ischaemic injury. Understanding the fundamental molecular pathways and pathophysiology of kidney injury and AKI in Covid‐19 is necessary to develop management strategies and design effective therapies.

Colorectal cancer (CRC) is the third most frequent cancer in human beings and is also the major cause of death among the other gastrointestinal cancers. The exact mechanisms of CRC development in most patients remains unclear. So far, several genetically, environmental and epigenetically risk factors have been identified for CRC development. The circadian rhythm is a 24-h rhythm that drives several biologic processes. The circadian system is guided by a central pacemaker which is located in the suprachiasmatic nucleus (SCN) in the hypothalamus. Circadian rhythm is regulated by circadian clock genes, cytokines and hormones like melatonin. Disruptions in biological rhythms are known to be strongly associated with several diseases, including cancer. The role of the different circadian genes has been verified in various cancers, however, the pathways of different circadian genes in the pathogenesis of CRC are less investigated. Identification of the details of the pathways in CRC helps researchers to explore new therapies for the malignancy.

Psychrotrophs or psychrophiles are extremophilic microorganisms that have the maximum temperature above 20 °C for growth. Since around 70% of the earth's biosphere temperature is below 5 °C, psychrotrophs could be found in diversity of species. These bacteria are source of enzymes, mainly including proteases used in different food industries where main reactions should be proceeded in low temperatures to save the aroma and flavor of food materials and bioactivity of valuable food ingredients such as bioactive peptides. Proteases are among the major groups of industrial enzymes accounting for 60% of the total global trade of enzymes. In this review, at first, we describe the biology, classification and physiological functions of different proteases obtained from psychrotrophic bacteria. Then, we present the various methods to produce and purify these enzymes from the bacteria. Moreover, we discuss several applications of the proteases to produce bioactive peptides from versatile protein sources. A comprehensive introduction to different types of proteases and their production and purification methods could help researchers identify novel proteases with improved properties, considering that their total market is significantly growing every year.

Purpose: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an identified human oncoprotein which modulates malignant cell growth. It is overexpressed in human prostate cancer and in most of the human malignancies. The aim of this study was to investigate the effects of CIP2A silencing on the sensitivity of PC-3 prostate cancer cells to docetaxel chemotherapy. Methods: PC-3 cells were transfected using CIP2A siRNA. CIP2A mRNA and protein expression were assessed after CIP2A gene silencing using q-RT PCR and Western blotting. Proliferation and apoptosis were analyzed after treatment with docetaxol using MTT assay, DAPI staining, and flow cytometry, respectively. Results: Silencing of CIP2A enhanced the sensitivity of PC-3 cells to docetaxel by strengthening docetaxel induced cell growth inhibition and apoptosis against PC-3 cells. Conclusion: Silencing of CIP2A may potentiate the cytotoxic effects of docetaxel and this might be a promising therapeutic approach in prostate cancer treatment.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a characterized human oncoprotein that is able to promote cancer cells proliferation, anchorage-independent cell growth and resistance to apoptosis. CIP2A inactivates protein phosphatase 2A (PP2A) which down-regulates Akt (Protein Kinase B) phosphorylation and stabilizes c-Myc (c-Myc oncogene product) in cancer cells. CIP2A has been studied in the most of human malignancies. Here we discuss the role of CIP2A in cancer and give a summary of CIP2A expression in malignancies. Also, where available we indicated the association of CIP2A with the stage of cancers and patients prognosis, explain its localization and the possibility of targeting CIP2A in different cancers.

Pancreatic cancer is related to a very weak diagnosis; the close parallel between disease incidence and mortality rates from pancreatic cancer reflects the fatal nature of this disease. Although early detection procedures are growing, they are not applicable yet for pancreatic cancer. The majority of cancer patients suffer from advanced disease, in which surgery has no potential effect. Based on the growing evidence, it is predicated that cancer immunotherapy alone or in combination will probably be an essential section of different cancer treatment methods. There are different kinds of immune processes, including various antitumour and tumour-promoting leukocytes. Moreover, tumour cells utilise numerous approaches to overwhelm the immune response. Use of antibody in the therapeutic protocols is proving significant success and is probably a key element of cancer treatment. This method is directed against numerous negative immunologic regulators and immune checkpoints. In the present review, the clinical outlines of immune checkpoint inhibition are discussed in pancreatic cancer.

Multifaceted cellular pathways exhibit a crucial role in the preservation of homeostasis at the molecular, cellular, and organism levels. One of the most important of these protective cascades is Nuclear factor E2-related factor (Nrf-2) that regulates the expression of several genes responsible for cellular detoxification, antioxidant function, anti-inflammation, drug/xenobiotic transportation, and stress-related factors. A growing body of evidence provides information regarding the protective role of Nrf-2 against a number of kidney diseases. Acute kidney injury (AKI) is a substantial clinical problem that causes a huge social burden. In the kidneys, Nrf-2 exerts a dynamic role in improving the injury triggered by inflammation and oxidative stress. Understanding of the exact molecular mechanisms underlying AKI is vital in order to determine the equilibrium between renal adaptation and malfunction and thus reduce disease progression. This review highlights the role of Nrf-2 targeting against AKI and provides evidence that targeting Nrf-2 to prevail oxidative damage and its consequences might exhibit protective effects in kidney diseases.

Context Immunotherapy is among the most promising modalities for treatment of cancer. Recently, interleukin 12 (IL-12) has been used as an immunotherapeutic agent in cancer gene therapy. IL-12 can activate dendritic cells (DCs) and boost anti-tumor immune responses. Objective In the current study, we have investigated if IL-12 gene therapy can lead to the regression of tumor mass in a mouse model of fibrosarcoma. Material and methods To investigate the therapeutic efficacy of IL-12, WEHI-164 tumor cells were transfected with murine-IL12 plasmids using Lipofectamine. Enzyme linked immunosorbent assay (ELISA) was used to confirm IL-12 expression in transfected cells. The fibrosarcoma mouse model was established by subcutaneous injection of transfected cells to Balb/C mice. Mice were sacrificed and the tumors were extracted. Tumor sizes were measured by caliper. The expression of IL-12 and IFN-γ was studied with real-time PCR and western blotting. The expression of Ki-67(a tumor proliferation marker) in tumor mass was studied by immunohistochemistry staining. Results and discussion The group treated with IL-12 showed a significant decrease in tumor mass volume (P: 0.000). The results of real-time PCR and western blotting showed that IL-12 and IFN-γ expression increased in the group treated with IL-12 (relative expression of IL-12: 1.9 and relative expression of IFN-γ: 1.766). Immunohistochemistry staining showed that Ki-67 expression was reduced in the group treated with IL-12. Conclusion IL-12 gene therapy successfully led to regress of tumor mass in the fibrosarcoma mouse model. This may serve as a candidate therapeutic approach for treatment of cancer.

Background: Interleukin (IL-12) and the granulocyte-monocyte colony-stimulating factor gene (GM-CSF) have been used as immunotherapeutic agents in cancer gene therapy as they activate dendritic cells and boost anti-tumor immune responses. IL-12 and GM-CSF have different roles in anti-tumor immune response. Objectives: The aim of present study was to investigate the anti-tumor effects of combined gene therapy with GM-CSF and IL-12 in a fibrosarcoma mouse model. Methods: To investigate the combined therapeutic effect of GM-CSF and IL-12, WEHI 164 tumor cells were transfected with Murine GM-CSF (m-GM-CSF) and Murine IL-12 (m-IL-12) genes, using Lipofectamine. The fibrosarcoma mouse model was established by subcutaneous injection of transfected cells to Balb/c mice. Mice were sacrificed and the tumors were extracted. Tumor sizes were measured by caliper. The expression of GM-CSF, IL-12 and IFN-γ was studied by real-time PCR and immunoblotting. The expression of Ki-67 (a proliferation marker) in tumor masses was studied by immunohistochemistry staining. Results: The tumor size was reduced in IL-12 + GM-CSF group (P < 0.0001); the results of western blotting and real-time PCR demonstrated that IL-12, GM-CSF and IFN-γ expression increased in IL-12+GM-CSF group (with a relative expression of: 2.86, 1.98, and 2.560). Immunohistochemistry staining indicated that Ki-67 expression was reduced in IL-12 + GM-CSF group. Conclusions: Combination therapy with GM-CSF and IL-12 displayed significant therapeutic effects and represented a promising gene therapy strategy for cancer.