Investigating the trend of demographic changes, mortality, clinical and paraclinical findings of patients hospitalized in the Corona ward, before and after the start of general vaccination of COVID-19.

BACKGROUND: Prioritizing prevention over treatment has been a longstanding principle in the world health system. This study aims to compare the demographic changes, mortality, clinical, and paraclinical findings of patients hospitalized in the Corona ward before and after the start of general vaccination. METHODS: This cross-sectional study utilized the simple random sampling method in 2022, analyzing 300 medical records of patients admitted to the Corona ward at 22 Bahman Khaf Hospital. Data were collected using a checklist with the help of the Medical Care Monitoring System and analyzed using SPSS-22 statistical software and Chi-square statistical test at a significance level of p < 0.05. RESULTS: Before the start of general vaccination for COVID-19, the majority of patients were hospitalized in the Corona Intensive Care Unit (59.3%), aged between 51 and 65 years (47.3%), hospitalized for more than 3 days (54%), required intubation (49.3%), had SPO2 < 93% (60.7%), and exhibited common symptoms such as cough, shortness of breath, and loss of consciousness. Paraclinical findings included positive CRP, decreased lymphocytes, and ground glass opacity (GGO). After the start of general vaccination for COVID-19, most patients were hospitalized in the general care department of Corona (68%), aged between 36 and 50 years (47.3%), hospitalized for less than three days (66%), required intubation (20%), had SPO2 ≥ 93% (77.3%), and exhibited common symptoms such as weakness, headache, and body pain. Paraclinical findings were within the normal range. CONCLUSIONS: General vaccination for COVID-19 has significantly reduced patient mortality and morbidity. Health policymakers should prioritize general vaccination to achieve herd immunity and improve public health.

STAT3 as a newly emerging target in colorectal cancer therapy: Tumorigenesis, therapy response, and pharmacological/nanoplatform strategies.

Colorectal cancer (CRC) ranks as the third most aggressive tumor globally, and it can be categorized into two forms: colitis-mediated CRC and sporadic CRC. The therapeutic approaches for CRC encompass surgical intervention, chemotherapy, and radiotherapy. However, even with the implementation of these techniques, the 5-year survival rate for metastatic CRC remains at a mere 12-14%. In the realm of CRC treatment, gene therapy has emerged as a novel therapeutic approach. Among the crucial molecular pathways that govern tumorigenesis, STAT3 plays a significant role. This pathway is subject to regulation by cytokines and growth factors. Once translocated into the nucleus, STAT3 influences the expression levels of factors associated with cell proliferation and metastasis. Literature suggests that the upregulation of STAT3 expression is observed as CRC cells progress towards metastatic stages. Consequently, elevated STAT3 levels serve as a significant determinant of poor prognosis and can be utilized as a diagnostic factor for cancer patients. The biological and malignant characteristics of CRC cells contribute to low survival rates in patients, as the upregulation of STAT3 prevents apoptosis and promotes pro-survival autophagy, thereby accelerating tumorigenesis. Furthermore, STAT3 plays a role in facilitating the proliferation of CRC cells through the stimulation of glycolysis and promoting metastasis via the induction of epithelial-mesenchymal transition (EMT). Notably, an intriguing observation is that the upregulation of STAT3 can mediate resistance to 5-fluorouracil, oxaliplatin, and other anti-cancer drugs. Moreover, the radio-sensitivity of CRC diminishes with increased STAT3 expression. Compounds such as curcumin, epigallocatechin gallate, and other anti-tumor agents exhibit the ability to suppress STAT3 and its associated pathways, thereby impeding tumorigenesis in CRC. Furthermore, it is worth noting that nanostructures have demonstrated anti-proliferative and anti-metastatic properties in CRC.

Eco-friendly chitosan-based nanostructures in diabetes mellitus therapy: Promising bioplatforms with versatile therapeutic perspectives.

Nature-derived polymers, or biopolymers, are among the most employed materials for the development of nanocarriers. Chitosan (CS) is derived from the acetylation of chitin, and this biopolymer displays features such as biocompatibility, biodegradability, low toxicity, and ease of modification. CS-based nano-scale delivery systems have been demonstrated to be promising carriers for drug and gene delivery, and they can provide site-specific delivery of cargo. Owing to the high biocompatibility of CS-based nanocarriers, they can be used in the future in clinical trials. On the other hand, diabetes mellitus (DM) is a chronic disease that can develop due to a lack of insulin secretion or insulin sensitivity. Recently, CS-based nanocarriers have been extensively applied for DM therapy. Oral delivery of insulin is the most common use of CS nanoparticles in DM therapy, and they improve the pharmacological bioavailability of insulin. Moreover, CS-based nanostructures with mucoadhesive features can improve oral bioavailability of insulin. CS-based hydrogels have been developed for the sustained release of drugs and the treatment of DM complications such as wound healing. Furthermore, CS-based nanoparticles can mediate delivery of phytochemicals and other therapeutic agents in DM therapy, and they are promising compounds for the treatment of DM complications, including nephropathy, neuropathy, and cardiovascular diseases, among others. The surface modification of nanostructures with CS can improve their properties in terms of drug delivery and release, biocompatibility, and others, causing high attention to these nanocarriers in DM therapy.

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.

Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial-mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC.

NF-κB as a regulator of cancer metastasis and therapy response: A focus on epithelial-mesenchymal transition.

Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival and prognosis of cancer patients. The epithelial-to-mesenchymal transition (EMT) is a well-known mechanism responsible for the invasiveness of tumor cells. A number of molecular pathways can regulate the EMT mechanism in cancer cells and nuclear factor-kappaB (NF-κB) is one of them. The nuclear translocation of NF-κB p65 can induce the transcription of several genes involved in EMT induction. The present review describes NF-κB and EMT interaction in cancer cells and their association in cancer progression. Due to the oncogenic role NF-κB signaling, its activation enhances metastasis of tumor cells via EMT induction. This has been confirmed in various cancers including brain, breast, lung and gastric cancers, among others. The ZEB1/2, transforming growth factor-ß, and Slug as inducers of EMT undergo upregulation by NF-κB to promote metastasis of tumor cells. After EMT induction driven by NF-κB, a significant decrease occurs in E-cadherin levels, while N-cadherin and vimentin levels undergo an increase. The noncoding RNAs can potentially also function as upstream mediators and modulate NF-κB/EMT axis in cancers. Moreover, NF-κB/EMT axis is involved in mediating drug resistance in tumor cells. Thus, suppressing NF-κB/EMT axis can also promote the sensitivity of cancer cells to chemotherapeutic agents.

The impact of education through nurse-led telephone follow-up (telenursing) on the quality of life of COVID-19 patients.

BACKGROUND: The widespread prevalence of COVID-19 has disrupted the social life, physical function, and daily activities of patients, leading to reduced quality of their lives. Because of the nature of this disease and its comprehensive impact on patients' lives, a follow-up based on the conditions of these patients is necessary. This study was conducted to determine the impact of nurse education and telephone follow-up (telenursing) on the quality of life of COVID-19 patients. METHODS: This quasi-experimental study included 120 COVID-19 patients discharged from 22nd-Bahman Hospital in Khaf city and was conducted over 6 months from July 20, 2020, to December 20, 2020. The participants were selected by convenience sampling method and were assigned into two matching groups. The training was delivered through telenursing based on the quality of life criteria for 1 month in the intervention group. The controls did not receive any intervention. Both groups completed the 36-item SF health survey before and 1 month after the intervention. RESULTS: The two groups were not significantly different regarding the quality of life mean scores at baseline (p = 0.61). However, after the intervention, the mean and standard deviation of the total life quality score was significantly different between the control and intervention groups (63.62 ± 3.93 versus 72.62 ± 3.51, p <0.001). CONCLUSIONS: Telenursing improves the life quality of COVID-19 patients. Through appropriate policies, health managers may put on the agenda the implementation of telenursing for COVID-19 patients.

Identifying factors affecting a healthy lifestyle in the post-COVID-19 era.

BACKGROUND: A healthy lifestyle is one of the important global concepts in the post-COVID-19 era, which can lead to maintaining and improving the health of societies. This study aimed to identify the factors affecting a healthy lifestyle in the post-COVID-19 era. MATERIALS AND METHODS: The current research is a qualitative study that was conducted in the field by theoretical sampling method. The qualitative method used in the current research was Strauss-Corbin's method. The data collection tool in the current research was a semi-structured interview. The researcher reached theoretical saturation by the end of the 13th interview, and for more certainty, the interviews continued until the 15th interview. The statistical population of the research was all professors and experts with specialized doctorate degrees in Mashhad University of Medical Sciences, and finally, 15 people were selected according to the entry and exit criteria for the study. Data analysis was done by summarizing and coding and analyzing the hidden content from expert interviews using MAXQDA software. RESULTS: The factors affecting a healthy lifestyle in the post-COVID-19 era (cultural norms, social norms, biological norms, technological factors, and economic factors) emerged from the intuitive opinions of experts. CONCLUSION: Providing and maintaining health is not a simple task, as it involves biological, individual, familial, cultural, societal, economic, political, and health factors. Promotion of healthy lifestyles is not merely the responsibility of health-related organizations and bodies; rather, they necessitate extensive coordination and empathy among educational, health, cultural, service, and even political institutions and bodies.

A comprehensive review of the PTEN/PI3K/Akt axis in multiple myeloma: From molecular interactions to potential therapeutic targets.

Phosphatase and tensin homolog (PTEN), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) signaling pathways contribute to the development of several cancers, including multiple myeloma (MM). PTEN is a tumor suppressor that influences the PI3K/Akt/mTOR pathway, which in turn impacts vital cellular processes like growth, survival, and treatment resistance. The current study aims to present the role of PTEN and PI3K/Akt/mTOR signaling in the development of MM and its response to treatment. In addition, the molecular interactions in MM that underpin the PI3K/Akt/mTOR pathway and address potential implications for the development of successful treatment plans are also discussed in detail. We investigate their relationship to both upstream and downstream regulators, highlighting new developments in combined therapies that target the PTEN/PI3K/Akt axis to overcome drug resistance, including the use of PI3K and mitogen-activated protein kinase (MAPK) inhibitors. We also emphasize that PTEN/PI3K/Akt pathway elements may be used in MM diagnosis, prognosis, and therapeutic targets.

The multifaceted role of SOX2 in breast and lung cancer dynamics.

Breast and lung cancers are leading causes of death among patients, with their global mortality and morbidity rates increasing. Conventional treatments often prove inadequate due to resistance development. The alteration of molecular interactions may accelerate cancer progression and treatment resistance. SOX2, known for its abnormal expression in various human cancers, can either accelerate or impede cancer progression. This review focuses on examining the role of SOX2 in breast and lung cancer development. An imbalance in SOX2 expression can promote the growth and dissemination of these cancers. SOX2 can also block programmed cell death, affecting autophagy and other cell death mechanisms. It plays a significant role in cancer metastasis, mainly by regulating the epithelial-to-mesenchymal transition (EMT). Additionally, an imbalanced SOX2 expression can cause resistance to chemotherapy and radiation therapy in these cancers. Genetic and epigenetic factors may affect SOX2 levels. Pharmacologically targeting SOX2 could improve the effectiveness of breast and lung cancer treatments.

Biological landscape and nanostructural view in development and reversal of oxaliplatin resistance in colorectal cancer.

The treatment of cancer patients has been mainly followed using chemotherapy and it is a gold standard in improving prognosis and survival rate of patients. Oxaliplatin (OXA) is a third-platinum anti-cancer agent that reduces DNA synthesis in cancer cells to interfere with their growth and cell cycle progression. In spite of promising results of using OXA in cancer chemotherapy, the process of drug resistance has made some challenges. OXA is commonly applied in treatment of colorectal cancer (CRC) as a malignancy of gastrointestinal tract and when CRC cells increase their proliferation and metastasis, they can obtain resistance to OXA chemotherapy. A number of molecular factors such as CHK2, SIRT1, c-Myc, LATS2 and FOXC1 have been considered as regulators of OXA response in CRC cells. The non-coding RNAs are able to function as master regulator of other molecular pathways in modulating OXA resistance. There is a close association between molecular mechanisms such as apoptosis, autophagy, glycolysis and EMT with OXA resistance, so that apoptosis inhibition, pro-survival autophagy induction and stimulation of EMT and glycolysis can induce OXA resistance in CRC cells. A number of anti-tumor compounds including astragaloside IV, resveratrol and nobiletin are able to enhance OXA sensitivity in CRC cells. Nanoparticles for increasing potential of OXA in CRC suppression and reversing OXA resistance have been employed in cancer chemotherapy. These subjects are covered in this review article to shed light on molecular factors resulting in OXA resistance.

Non-coding RNA-Mediated N6-Methyladenosine (m6A) deposition: A pivotal regulator of cancer, impacting key signaling pathways in carcinogenesis and therapy response.

The emergence of RNA modifications has recently been considered as critical post-transcriptional regulations which governed gene expression. N6-methyladenosine (m6A) modification is the most abundant type of RNA modification which is mediated by three distinct classes of proteins called m6A writers, readers, and erasers. Accumulating evidence has been made in understanding the role of m6A modification of non-coding RNAs (ncRNAs) in cancer. Importantly, aberrant expression of ncRNAs and m6A regulators has been elucidated in various cancers. As the key role of ncRNAs in regulation of cancer hallmarks is well accepted now, it could be accepted that m6A modification of ncRNAs could affect cancer progression. The present review intended to discuss the latest knowledge and importance of m6A epigenetic regulation of ncRNAs including mircoRNAs, long non-coding RNAs, and circular RNAs, and their interaction in the context of cancer. Moreover, the current insight into the underlying mechanisms of therapy resistance and also immune response and escape mediated by m6A regulators and ncRNAs are discussed.

EZH2 as a potential therapeutic target for gastrointestinal cancers.

Gastrointestinal (GI) cancers continue to be a major cause of mortality and morbidity globally. Understanding the molecular pathways associated with cancer progression and severity is essential for creating effective cancer treatments. In cancer research, there is a notable emphasis on Enhancer of zeste homolog 2 (EZH2), a key player in gene expression influenced by its irregular expression and capacity to attach to promoters and alter methylation status. This review explores the impact of EZH2 signaling on various GI cancers, such as colorectal, gastric, pancreatic, hepatocellular, esophageal, and cholangiocarcinoma. The primary function of EZH2 signaling is to facilitate the accelerated progression of cancer cells. Additionally, EZH2 has the capacity to modulate the reaction of GI cancers to chemotherapy and radiotherapy. Numerous pathways, including long non-coding RNAs and microRNAs, serve as upstream regulators of EZH2 in these types of cancer. EZH2's enzymatic activity enables it to attach to target gene promoters, resulting in methylation that modifies their expression. EZH2 could be considered as an independent prognostic factor, with increased expression correlating with a worse disease prognosis. Additionally, a range of gene therapies including small interfering RNA, and anti-tumor agents are being explored to target EZH2 for cancer treatment. This comprehensive review underscores the current insights into EZH2 signaling in gastrointestinal cancers and examines the prospect of therapies targeting EZH2 to enhance patient outcomes.

Shedding light on function of long non-coding RNAs (lncRNAs) in glioblastoma.

The brain tumors and especially glioblastoma, are affecting life of many people worldwide and due to their high mortality and morbidity, their treatment is of importance and has gained attention in recent years. The abnormal expression of genes is commonly observed in GBM and long non-coding RNAs (lncRNAs) have demonstrated dysregulation in this tumor. LncRNAs have length more than 200 nucleotides and they have been located in cytoplasm and nucleus. The current review focuses on the role of lncRNAs in GBM. There two types of lncRNAs in GBM including tumor-promoting and tumor-suppressor lncRNAs and overexpression of oncogenic lncRNAs increases progression of GBM. LncRNAs can regulate proliferation, cell cycle arrest and metastasis of GBM cells. Wnt, STAT3 and EZH2 are among the molecular pathways affected by lncRNAs in GBM and for regulating metastasis of GBM cells, these RNA molecules mainly affect EMT mechanism. LncRNAs are involved in drug resistance and can induce resistance of GBM cells to temozolomide chemotherapy. Furthermore, lncRNAs stimulate radio-resistance in GBM cells. LncRNAs increase PD-1 expression to mediate immune evasion. LncRNAs can be considered as diagnostic and prognostic tools in GBM and researchers have developed signature from lncRNAs in GBM.

Biological and therapeutic viewpoints towards role of miR-218 in human cancers: Revisiting molecular interactions and future clinical translations.

Understanding the exact pathogenesis of cancer is difficult due to heterogenous nature of tumor cells and multiple factors that cause its initiation and development. Treatment of cancer is mainly based on surgical resection, chemotherapy, radiotherapy and their combination, while gene therapy has been emerged as a new kind of therapy for cancer. Post-transcriptional regulation of genes has been of interest in recent years and among various types of epigenetic factors that can modulate gene expression, short non-coding RNAs known as microRNAs (miRNAs) have obtained much attention. The stability of mRNA decreases by miRNAs to repress gene expression. miRNAs can regulate tumor malignancy and biological behavior of cancer cells and understanding their function in tumorigenesis can pave the way towards developing new therapeutics in future. One of the new emerging miRNAs in cancer therapy is miR-218 that increasing evidence highlights its anti-cancer activity, while a few studies demonstrate its oncogenic function. The miR-218 transfection is promising in reducing progression of tumor cells. miR-218 shows interactions with molecular mechanisms including apoptosis, autophagy, glycolysis and EMT, and the interaction is different. miR-218 induces apoptosis, while it suppresses glycolysis, cytoprotective autophagy and EMT. Low expression of miR-218 can result in development of chemoresistance and radio-resistance in tumor cells and direct targeting of miR-218 as a key player is promising in cancer therapy. LncRNAs and circRNAs are nonprotein coding transcripts that can regulate miR-218 expression in human cancers. Moreover, low expression level of miR-218 can be observed in human cancers such as brain, gastrointestinal and urological cancers that mediate poor prognosis and low survival rate.

STAT3 signaling in prostate cancer progression and therapy resistance: An oncogenic pathway with diverse functions.

The categorization of cancers demonstrates that prostate cancer is the most common malignancy in men and it causes high death annually. Prostate cancer patients are diagnosed mainly via biomarkers such as PSA test and patients show poor prognosis. Prostate cancer cells rapidly diffuse into different parts of body and their metastasis is also a reason for death. Current therapies for prostate cancer patients include chemotherapy, surgery and radiotherapy as well as targeted therapy. The progression of prostate cancer cells is regulated by different factors that STAT3 signaling is among them. Growth factors and cytokines such as IL-6 can induce STAT3 signaling and it shows carcinogenic impact. Activation of STAT3 signaling occurs in prostate cancer and it promotes malignant behavior of tumor cells. Induction of STAT3 signaling increases glycolysis and proliferation of prostate cancer cells and prevents apoptosis. Furthermore, STAT3 signaling induces EMT mechanism in increasing cancer metastasis. Activation of STAT3 signaling stimulates drug resistance and the limitation of current works is lack of experiment related to role of STAT3 signaling in radio-resistance in prostate tumor. Calcitriol, capsazepine and ß-elemonic are among the compounds capable of targeting STAT3 signaling and its inhibition in prostate cancer therapy. In addition to natural products, small molecules targeting STAT3 signaling have been developed in prostate cancer therapy.

miRNAs and exosomal miRNAs in lung cancer: New emerging players in tumor progression and therapy response.

Non-coding RNAs have shown key roles in cancer and among them, short RNA molecules are known as microRNAs (miRNAs). These molecules have length less than 25 nucleotides and suppress translation and expression. The functional miRNAs are produced in cytoplasm. Lung cancer is a devastating disease that its mortality and morbidity have undergone an increase in recent years. Aggressive behavior leads to undesirable prognosis and tumors demonstrate abnormal proliferation and invasion. In the present review, miRNA functions in lung cancer is described. miRNAs reduce/increase proliferation and metastasis. They modulate cell death and proliferation. Overexpression of oncogenic miRNAs facilitates drug resistance and radio-resistance in lung cancer. Tumor microenvironment components including macrophages and cancer-associated fibroblasts demonstrate interactions with miRNAs in lung cancer. Other factors such as HIF-1α, lncRNAs and circRNAs modulate miRNA expression. miRNAs have also value in the diagnosis of lung cancer. Understanding such interactions can pave the way for developing novel therapeutics in near future for lung cancer patients.

New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis.

Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance.

Non-coding RNAs in EMT regulation: Association with tumor progression and therapy response.

RNA molecules lacking capacity in protein translation, are known as non-coding RNAs (ncRNAs). Growth, differentiation and migration are influenced by ncRNAs in cells. The abnormal expression of ncRNAs contributes to development of diseases, especially cancer. On the other hand, EMT is a vital mechanism for cancer invasion and diffusion in body. In this manuscript, role of ncRNAs in EMT regulation and subsequent effect on cancer progression is investigated. The miRNAs regulate EMT by affecting signaling pathways including PI3K/Akt and PTEN to modulate cancer metastasis. Furthermore, miRNA and EMT interaction has close association with drug sensitivity of tumor cells. LncRNAs can affect EMT via targeting ZEB1/2, Twist and Snail among others and similarly, based on the impact on EMT, sensitivity of cancer cells to therapy increases or decreases. CircRNAs regulate both drug sensitivity and metastasis of cancers by affecting EMT mechanism. Noteworthy, circRNAs and lncRNAs are capable of sponging miRNAs in modulating EMT mechanism. Exosomes belong to extracellular vesicles with low size that can be secreted by cells in transferring genetic materials. The transfer of ncRNAs by exosomes is performed and they can also regulate EMT in cancer progression. Finally, ncRNAs regulating EMT mechanism are used for cancer diagnosis and prognosis.

Targeting Nrf2 in ischemia-reperfusion alleviation: From signaling networks to therapeutic targeting.

The nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of redox balance and it responds to various cell stresses that oxidative stress is the most well-known one. The Nrf2 should undergo nuclear translocation to exert its protective impacts and decrease ROS production. On the other hand, ischemic/reperfusion (I/R) injury is a pathological event resulting from low blood flow to an organ and followed by reperfusion. The I/R induces cell injury and organ dysfunction. The present review focuses on Nrf2 function in alleviation of I/R injury. Stimulating of Nrf2 signaling ameliorates I/R injury in various organs including lung, liver, brain, testis and heart. The Nrf2 enhances activity of antioxidant enzymes to reduce ROS production and prevent oxidative stress-mediated cell death. Besides, Nrf2 reduces inflammation via decreasing levels of pro-inflammatory factors including IL-6, IL-1ß and TNF-α. Nrf2 signaling is beneficial in preventing apoptosis and increasing cell viability. Nrf2 induces autophagy to prevent apoptosis during I/R injury. Furthermore, it can interact with other molecular pathways including PI3K/Akt, NF-κB, miRNAs, lncRNAs and GSK-3ß among others, to ameliorate I/R injury. The therapeutic agents, most of them are phytochemicals such as resveratrol, berberine and curcumin, induce Nrf2 signaling in I/R injury alleviation.

Targeting AMPK signaling in ischemic/reperfusion injury: From molecular mechanism to pharmacological interventions.

Ischemia is a pathological process in which blood supply to a particular organ is temporarily interrupted resulting in disturbed biological function and homeostasis of local tissues. Following ischemia, reperfusion and reoxygenation may occur which further worsens oxidative stress-mediated damage in cells and tissues. The combined processes are referred to as ischemia/reperfusion (I/R) injury. Immediate management and treatment of I/R is of utmost importance for preventing irreversible and extensive cellular damage. Apoptosis, inflammation and oxidative stress are the most validated pathologies associated with I/R. AMP-activated protein kinase (AMPK) modulates energy metabolism in cells and its activation occurs in response to elevated AMP and ADP levels. Aberrant levels of AMPK are noted in various pathological settings such as diabetes mellitus, cancer and neurological diseases. This review emphasizes AMPK signaling, its related molecular pathways and therapeutic utility during I/R. Activation of AMPK through phosphorylation prevents apoptosis and reduces oxidative stress and inflammation upon I/R. Inducing AMPK signaling normalizes mitochondrial function to inhibit cell death. Autophagy as a cytoprotective mechanism undergoes activation by AMPK/mTOR and AMPK/ULK1 pathways. AMPK reinforces the antioxidant defense capacity via Nrf2 signaling to counteract oxidative stress in I/R. Protective compounds including phytochemicals activate AMPK to alleviate I/R injury.