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Abstract Background Fracture of the femur is one of the most common fractures that, if not stabilized and treated properly, may lead to severe disability, impairment of the individual’s efficiency, and numerous complications. This study aimed to evaluate the treatment results of femoral shaft fracture with two methods intramedullary nail (IMN) and Plate. Materials and methods In this cross-sectional study, 60 patients with femoral bone fractures were admitted to Imam Khomeini Hospital in Jiroft in 2020 and were treated for at least one year after discharge. They were divided into two treatment groups - Plate fracture fixation (n = 30) and IMN fracture fixation (n = 30). Data were collected using a researcher-made checklist including patient demographics and treatment outcomes. The collected data were analyzed using SPSS-v 26 statistical software and descriptive and inferential statistical tests at a significance level of p

Abstract Background Various treatment approaches for individuals with ankle sprains can reduce treatment costs and enhance recovery. This study aimed to compare the efficacy of spring ankle braces with splints and casts in treating ankle sprains. Materials and methods This cross-sectional study involved 60 patients diagnosed with ankle sprains at the orthopedic clinic of Imam Khomeini Hospital in Jiroft in 2022. Following diagnosis confirmation through additional examinations and imaging, patients with ankle sprains not requiring surgery were selected and placed in two groups: one treated with spring ankle braces and the other with splints or casts. Both groups underwent a 4-week treatment regimen, comprising 30 individuals each. Data were collected and analyzed using SPSS version 26. Results The average age of patients was 32.5 ± 13.4 years. Of the ankle sprain patients, 56.7% were male. Patients reported the highest satisfaction levels with the plaster cast treatment method. A statistically significant relationship was found between patient satisfaction and the treatment methods of spring ankle braces and plaster casting (P

The complex interplay of epigenetic factors is essential in regulating the hallmarks of cancer and orchestrating intricate molecular interactions during tumor progression. Circular RNAs (circRNAs), known for their covalently closed loop structures, are non-coding RNA molecules exceptionally resistant to enzymatic degradation, which enhances their stability and regulatory functions in cancer. Similarly, microRNAs (miRNAs) are endogenous non-coding RNAs with linear structures that regulate cellular biological processes akin to circRNAs. Both miRNAs and circRNAs exhibit aberrant expressions in various cancers. Notably, circRNAs can function as sponges for miRNAs, influencing their activity. The circRNA/miRNA interaction plays a pivotal role in the regulation of cancer progression, including in brain, gastrointestinal, gynecological, and urological cancers, influencing key processes such as proliferation, apoptosis, invasion, autophagy, epithelial-mesenchymal transition (EMT), and more. Additionally, this interaction impacts the response of tumor cells to radiotherapy and chemotherapy and contributes to immune evasion, a significant challenge in cancer therapy. Both circRNAs and miRNAs hold potential as biomarkers for cancer prognosis and diagnosis. In this review, we delve into the circRNA-miRNA circuit within human cancers, emphasizing their role in regulating cancer hallmarks and treatment responses. This discussion aims to provide insights for future research to better understand their functions and potentially guide targeted treatments for cancer patients using circRNA/miRNA-based strategies.

Ferroptosis, a recently identified type of non-apoptotic cell death, triggers the elimination of cells in the presence of lipid peroxidation and in an iron-dependent manner. Indeed, ferroptosis-stimulating factors have the ability of suppressing antioxidant capacity, leading to the accumulation of reactive oxygen species (ROS) and the subsequent oxidative death of the cells. Ferroptosis is involved in the pathophysiological basis of different maladies, such as multiple cancers, among which female-oriented malignancies have attracted much attention in recent years. In this context, it has also been unveiled that non-coding RNA transcripts, including microRNAs, long non-coding RNAs, and circular RNAs have regulatory interconnections with the ferroptotic flux, which controls the pathogenic development of diseases. Furthermore, the potential of employing these RNA transcripts as therapeutic targets during the onset of female-specific neoplasms to modulate ferroptosis has become a research hotspot; however, the molecular mechanisms and functional alterations of ferroptosis still require further investigation. The current review comprehensively highlights ferroptosis and its association with non-coding RNAs with a focus on how this crosstalk affects the pathogenesis of female-oriented malignancies, from breast cancer to ovarian, cervical, and endometrial neoplasms, suggesting novel therapeutic targets to decelerate and even block the expansion and development of these tumors.

As the deadliest type of primary brain tumor, gliomas represent a significant worldwide health concern. Circular RNA (circRNA), a unique non-coding RNA molecule, seems to be one of the most alluring target molecules involved in the pathophysiology of many kinds of cancers. CircRNAs have been identified as prospective targets and biomarkers for the diagnosis and treatment of numerous disorders, particularly malignancies. Recent research has established a clinical link between temozolomide (TMZ) resistance and certain circRNA dysregulations in glioma tumors. CircRNAs may play a therapeutic role in controlling or overcoming TMZ resistance in gliomas and may provide guidance for a novel kind of individualized glioma therapy. To address the biological characteristics of circRNAs and their potential to induce resistance to TMZ, this review has highlighted and summarized the possible roles that circRNAs may play in molecular pathways of drug resistance, including the Ras/Raf/ERK PI3K/Akt signaling pathway and metabolic processes in gliomas.

Objective: Autophagy, as a cellular pathway involved inremoving damaged proteins and organelles, performs a vitalfunction in the homeostasis and fate of cells. Natural compoundsof coumarin (CO) are found in a variety of herbs. Due to theirmany medicinal properties, including antitumor and antiproliferative activity, they are involved in apoptosis and autophagyprocesses. This investigation desired to analyze the apoptotic andautophagic effects of p-coumaric acid (PCA) and CO on HT-29cells cultured in fibrin hydrogel.Materials and Methods: Cell viability and apoptotic andautophagic changes were evaluated by MTT assay, AcridineOrange, 4′,6-diamidino-2-phenylindole (DAPI), andmonodansylcadaverine (MDC) staining. The expression Bax, Bad,Bcl2, Lc3, Beclin-1, P53 and Atg5 was respectively measured byqRT-PCR and Western blotting.Results: CO (IC50=25 μM) and PCA (IC50=150 μM) had a doseand time-dependent cytotoxic effect in HT-29 cells. So, thecytotoxic effects of CO were significantly higher than PCA andthese differences were also evident in cell morphologyinvestigations. The data illustrated a high expression of proapoptotic and pro-autophagic genes and a declined expression ofanti-apoptotic and anti-autophagic genes.Conclusion: CO (that was more potent) and p-coumaric acidinduced autophagy via PI3K/Akt/mTOR and AMPK/mTORsignaling on HT-29 cells.

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.

Mitophagy, the cellular process of selectively eliminating damaged mitochondria, plays a crucial role in maintaining metabolic balance and preventing insulin resistance, both key factors in type 2 diabetes mellitus (T2DM) development. When mitophagy malfunctions in diabetic neuropathy, it triggers a cascade of metabolic disruptions, including reduced energy production, increased oxidative stress, and cell death, ultimately leading to various complications. Thus, targeting mitophagy to enhance the process may have emerged as a promising therapeutic strategy for T2DM and its complications. Notably, plant-derived compounds with β-cell protective and mitophagy-stimulating properties offer potential as novel therapeutic agents. This review highlights the intricate mechanisms linking mitophagy dysfunction to T2DM and its complications, particularly neuropathy, elucidating potential therapeutic interventions for this debilitating disease.

Abstract Background and Aim Helicobacter pylori plays an important role in causing digestive diseases. The purpose of this study is to investigate Helicobacter pylori in COVID‐19 patients with and without gastrointestinal symptoms. Methods In this case–control study, all patients with COVID‐19 admitted to Imam Khomeini Hospital in Jiroft city in 2021 were convenience sampled and divided into two homogeneous groups. Ninety‐five patients with COVID‐19, who presented with gastrointestinal symptoms, were included in the case group, while 95 patients with COVID‐19 without gastrointestinal symptoms were included in the control group. Noninvasive diagnostic methods, including serology and stool antigen tests, were used to identify Helicobacter pylori in the studied patients. Results Fifty‐three people (55.8%) from the case group had Helicobacter pylori, and 48 (50.5%) from the control group had Helicobacter pylori. Among the 53 people from the case group, 27 (50.9%) were men and 26 (49.1%) were women. Nineteen people (35.8%) were taking pantoprazole, 10 people (18.8%) were taking nonsteroidal anti‐inflammatory drugs, 20 people (37.7%) were taking narcotics, and 7 people (13.2%) had peptic ulcer. Seven people (13.2%) had an H2 blocker, and 21 people had an underlying disease. A significant relationship between infection with Helicobacter pylori and the use of pantoprazole, nonsteroidal anti‐inflammatory drugs, narcotics, peptic ulcer, underlying disease, and H2 blocker in COVID‐19 patients with gastrointestinal symptoms and without gastrointestinal symptoms was present (P‐value

Abstract 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

Introduction: Various pieces of evidence suggest an elevation in the levels of EGFR and HER2 in different cancers leading to the proliferation, invasion, and metastasis of cancer cells. In this study, we conducted a comprehensive investigation into the expression alterations of these two receptors in various cancers using in silico data. In addition, we investigated the therapeutic potential of lapatinib as an inhibitor of these receptors in various cancer types. Methods: RNAseq data for prevalent cancers were downloaded from The Cancer Genome Atlas (TCGA). After initial preprocessing, expression changes of HER2, EGFR, and candidate genes—identified based on their association with EGFR and HER2 signaling pathways—were examined. Human protein atlas data were utilized to assess the protein expression of HER2 and EGFR. GSE129254 was employed to identify molecular pathways and candidate genes associated with lapatinib. The protein-protein interaction network was used to identify lapatinib-influenced hub genes. Clinical data for common cancers were used to investigate the correlation between the expression of candidate genes and patients' mortality rates by Cox regression test. Results: The findings clearly indicated a significant increase in the expression levels of HER2 and EGFR in cancers such as kidney, lung, breast, bladder, pancreas, head and neck, stomach, and endometrial, both at the mRNA and protein levels (p-value

Abstract Nonviral vectors, such as liposomes, offer potential for targeted gene delivery in cancer therapy. Liposomes, composed of phospholipid vesicles, have demonstrated efficacy as nanocarriers for genetic tools, addressing the limitations of off‐targeting and degradation commonly associated with traditional gene therapy approaches. Due to their biocompatibility, stability, and tunable physicochemical properties, they offer potential in overcoming the challenges associated with gene therapy, such as low transfection efficiency and poor stability in biological fluids. Despite these advancements, there remains a gap in understanding the optimal utilization of nanoliposomes for enhanced gene delivery in cancer treatment. This review delves into the present state of nanoliposomes as carriers for genetic tools in cancer therapy, sheds light on their potential to safeguard genetic payloads and facilitate cell internalization alongside the evolution of smart nanocarriers for targeted delivery. The challenges linked to their biocompatibility and the factors that restrict their effectiveness in gene delivery are also discussed along with exploring the potential of nanoliposomes in cancer gene therapy strategies by analyzing recent advancements and offering future directions.

Background: Solute carrier (SLC) transporters, a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment (TME). Amino acids are fundamental building blocks of cells and play essential roles in protein synthesis, nutrient sensing, and oncogenic signaling pathways. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. Scope of Review: In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. Major Conclusions: Amino acids transportation by SLCs plays a critical role in tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although several studies evaluated the function of SLC7A11 and SLC1A5, the role of some SLC proteins in cancer is not studied well. To exert their functions, SLCs mediate metabolic rewiring, regulate the maintenance of redox balance, affect main oncogenic pathways, regulate amino acids bioavailability within the TME, and alter the sensitivity of cancer cells to therapeutics. However, different therapeutic methods that prevent the function of SLCs were able to inhibit tumor progression. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids and their transporters within the SLC superfamily.

Context: Dengue fever has been reported in 129 countries worldwide, including 100 countries in the Mediterranean region, South America, and Southeast Asia. It results in approximately 40,000 deaths each year, and there have been significant outbreaks of dengue fever in these areas in recent years. Approximately 50% of the global population is presently susceptible to acquiring the dengue virus, which is classified as an emerging and re-emerging ailment that is likely to impact several nations in the foreseeable future. Evidence Acquisition: Despite the significant harm inflicted upon human health and the economic conditions of countries in recent years, dengue continues to be classified as a neglected disease, without the requisite attention and concerted efforts by countries to effectively manage it. Any actions taken in this domain are inherently constrained. Consequently, due to the significance of dengue fever, this study aims to comprehensively examine this matter. Results: The disease used to be effectively managed in regions like the countries of the American continent and Singapore, but it has made a resurgence. Between 2008 and 2010, the number of cases in the regions of America, Southeast Asia, and the Western Pacific rose from 0.2 million to 2.2 million. These reports exclusively consist of officially documented sick cases. Multiple outbreaks have been documented in Asia, encompassing countries such as China, Pakistan, Taiwan, and Malaysia, as well as in South America, including Brazil and Mexico. Dengue fever cases have been documented in several Middle Eastern nations, including Yemen, Saudi Arabia, and southern Iran. Local transmission of the disease has begun in Europe, with France and Croatia reporting cases of local transmission. Annually, a minimum of 500,000 individuals experience serious illnesses requiring hospitalization. Approximately 2.5% of individuals who contract the condition die from it. Every year, numerous severe cases of dengue fever are documented, resulting in at least 20,000 deaths. Conclusion: Dengue fever is a complex systemic disease. Assessing the complete range of the disease burden of dengue fever will be crucial to properly comprehend the serious medical and economic repercussions it has on patients and the general public.

Diabetes mellitus (DM) is a metabolic illness defined by elevated blood glucose levels, mediating various tissue alterations, including the dysfunction of vital organs. Diabetes mellitus (DM) can lead to many consequences that specifically affect the brain, heart, and kidneys. These issues are known as neuropathy, cardiomyopathy, and nephropathy, respectively. Inflammation is acknowledged as a pivotal biological mechanism that contributes to the development of various diabetes consequences. NF-κB modulates inflammation and the immune system at the cellular level. Its abnormal regulation has been identified in several clinical situations, including cancer, inflammatory bowel illnesses, cardiovascular diseases, and Diabetes Mellitus (DM). The purpose of this review is to evaluate the potential impact of NF-κB on complications associated with DM. Enhanced NF-κB activity promotes inflammation, resulting in cellular harm and compromised organ performance. Phytochemicals, which are therapeutic molecules, can potentially decline the NF-κB level, therefore alleviating inflammation and the progression of problems correlated with DM. More importantly, the regulation of NF-κB can be influenced by various factors, such as TLR4 in DM. Highlighting these factors can facilitate the development of novel therapies in the future.

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.

As a clinically approved treatment strategy, chemotherapy-mediated tumor suppression has been compromised, and in spite of introducing various kinds of anticancer drugs, cancer eradication with chemotherapy is still impossible. Chemotherapy drugs have been beneficial in improving the prognosis of cancer patients, but after resistance emerged, their potential disappeared. Oxaliplatin (OXA) efficacy in tumor suppression has been compromised by resistance. Due to the dysregulation of pathways and mechanisms in OXA resistance, it is suggested to develop novel strategies for overcoming drug resistance. The targeted delivery of OXA by nanostructures is described here. The targeted delivery of OXA in cancer can be mediated by polymeric, metal, lipid and carbon nanostructures. The advantageous of these nanocarriers is that they enhance the accumulation of OXA in tumor and promote its cytotoxicity. Moreover, (nano)platforms mediate the co-delivery of OXA with drugs and genes in synergistic cancer therapy, overcoming OXA resistance and improving insights in cancer patient treatment in the future. Moreover, smart nanostructures, including pH-, redox-, light-, and thermo-sensitive nanostructures, have been designed for OXA delivery and cancer therapy. The application of nanoparticle-mediated phototherapy can increase OXA's potential in cancer suppression. All of these subjects and their clinical implications are discussed in the current review.

Abstract 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. Graphical Abstract

Background: Breast cancer (BC) has been identified as a significant contributor to the rising number of female cancer deaths. As, it has become clear that breast cancer development depends on the interplay of several biological factors against a single molecule. This research aimed to use proteomics to gain a regulatory and metabolic understanding of BC pathophysiology. Method: For the study, a breast cancer proteomics dataset was downloaded from ProteomeXchange and then analyzed by employing MaxQuant and Perseus. Functional enrichment analysis through Metascape and Cytoscape software showed DEPs related biomedical phenomena with potential abruption. The expression of selected lncRNA in terms of the highest connectivity parameters was then quantitatively assessed through RT-PCR in 30 tumor tissues of breast cancer patients, as compared to the adjacent healthy ones. Result: The results indicated that among the 3048 identified proteins, 1149 were differentially expressed, which could be mainly enriched in several key terms. Furthermore, the obtained findings revealed that ITGB1-DT was significantly overexpressed in tumor tissues. Moreover, we found five potential compounds that could be attributed to ITGB1-DT targets (ATN-161, Firategrast, SB-683698, dabigatran-etexilate, and tranexamic-acid). Conclusion: These analyses proposed that ITGB1-DT could be employed as a differentiated factor to identify breast tumor tissues in healthy samples. Besides this, Firategrast could be introduced as a potential remedial agent for breast cancer patients. Overall, from the analysis of a proteomics dataset, an integrative map was generated, and a novel biomarker that may have been implicated in the early detection of BC was introduced.

Abstract Background One of the most malignant tumors in men is prostate cancer that is still incurable due to its heterogenous and progressive natures. Genetic and epigenetic changes play significant roles in its development. The RNA molecules with more than 200 nucleotides in length are known as lncRNAs and these epigenetic factors do not encode protein. They regulate gene expression at transcriptional, post-transcriptional and epigenetic levels. LncRNAs play vital biological functions in cells and in pathological events, hence their expression undergoes dysregulation. Aim of review The role of epigenetic alterations in prostate cancer development are emphasized here. Therefore, lncRNAs were chosen for this purpose and their expression level and interaction with other signaling networks in prostate cancer progression were examined. Key scientific concepts of review The aberrant expression of lncRNAs in prostate cancer has been well-documented and progression rate of tumor cells are regulated via affecting STAT3, NF-κB, Wnt, PI3K/Akt and PTEN, among other molecular pathways. Furthermore, lncRNAs regulate radio-resistance and chemo-resistance features of prostate tumor cells. Overexpression of tumor-promoting lncRNAs such as HOXD-AS1 and CCAT1 can result in drug resistance. Besides, lncRNAs can induce immune evasion of prostate cancer via upregulating PD-1. Pharmacological compounds such as quercetin and curcumin have been applied for targeting lncRNAs. Furthermore, siRNA tool can reduce expression of lncRNAs thereby suppressing prostate cancer progression. Prognosis and diagnosis of prostate tumor at clinical course can be evaluated by lncRNAs. The expression level of exosomal lncRNAs such as lncRNA-p21 can be investigated in serum of prostate cancer patients as a reliable biomarker.

Abstract Cancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment. Graphical Abstract

High mobility group A 2 (HMGA2) is a protein that modulates the structure of chromatin in the nucleus. Importantly, aberrant expression of HMGA2 occurs during carcinogenesis, and this protein is an upstream mediator of cancer hallmarks including evasion of apoptosis, proliferation, invasion, metastasis, and therapy resistance. HMGA2 targets critical signaling pathways such as Wnt/β-catenin and mTOR in cancer cells. Therefore, suppression of HMGA2 function notably decreases cancer progression and improves outcome in patients. As HMGA2 is mainly oncogenic, targeting expression by non-coding RNAs (ncRNAs) is crucial to take into consideration since it affects HMGA2 function. MicroRNAs (miRNAs) belong to ncRNAs and are master regulators of vital cell processes, which affect all aspects of cancer hallmarks. Long ncRNAs (lncRNAs) and circular RNAs (circRNAs), other members of ncRNAs, are upstream mediators of miRNAs. The current review intends to discuss the importance of the miRNA/HMGA2 axis in modulation of various types of cancer, and mentions lncRNAs and circRNAs, which regulate this axis as upstream mediators. Finally, we discuss the effect of miRNAs and HMGA2 interactions on the response of cancer cells to therapy. Regarding the critical role of HMGA2 in regulation of critical signaling pathways in cancer cells, and considering the confirmed interaction between HMGA2 and one of the master regulators of cancer, miRNAs, targeting miRNA/HMGA2 axis in cancer therapy is promising and this could be the subject of future clinical trial experiments.

Introduction: The quality of drinking water is an important factor that may affect broiler performance. Water is very important resource for poultry and is mainly supplied from groundwater sources, rivers, and springs. In addition to being a nutrient, water also softens food and carries it through the body, aids in digestion and absorption, and cools the body as it evaporates through the bird’s lungs and air sacs. Water helps remove waste, lubricates joints, is a major component of blood, and a necessary medium for many chemical reactions that help form meat and eggs. This study discusses some of the most common factors that impact poultry farms water quality. Therefore, this study aimed to investigate the chemical quality of samples obtained from various sources of poultry drinking water in Noorabad city of Fars province and neighboring villages.Materials and Methods: This study is a cross-sectional study and was conducted for evaluating the quality of water used in poultry farms in Noorabad city of Fars province and neighboring villages such as Dam Qanat, Kol Gah, Gazargah, Arab Khalifa Sofla, Fahlian, Tal Kohneh, Mal Mahmoud and Bajgah. Total hardness, pH, total dissolved solids, chlorine, calcium, magnesium, and sodium of water in nine regions were evaluated. This study was conducted in the second quarter of 1399. Water sampling was done in 30 poultry farms with three replicates. For this purpose, three samplings were randomly taken from each poultry farm three times a month. The samples collected in plastic containers were immediately tested for pH and transferred to the laboratory for other experiments at room temperature. The sampled poultry farms used well water.Total hardness, pH, chlorine, calcium, and water magnesium were measured using a model 7500 photometer according to the device's instructions and APHA. Results were analyzed statistically by SPSS software version 20 and the One-way ANOVA test with the Duncan post hoc test. Mean ± SD was considered significant if (P

Abstract Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs family and can exert functional roles in cells due to its methyltransferase activity. EZH2 affects gene expression via inducing H3K27me3. In the present review, our aim is to provide a mechanistic discussion of ncRNAs role in regulating EZH2 expression in different cancers. MiRNAs can dually induce/inhibit EZH2 in cancer cells to affect downstream targets such as Wnt, STAT3 and EMT. Furthermore, miRNAs can regulate therapy response of cancer cells via affecting EZH2 signaling. It is noteworthy that EZH2 can reduce miRNA expression by binding to promoter and exerting its methyltransferase activity. Small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) are synthetic, short ncRNAs capable of reducing EZH2 expression and suppressing cancer progression. LncRNAs mainly regulate EZH2 expression via targeting miRNAs. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation.

Highlights • Prostate cancer is among the leading causes of death in men where targeting autophagy is of importance in treatment; • Autophagy governs proliferation and metastasis capacity of prostate cancer cells; • Autophagy modulation is of interest in improving the therapeutic response of prostate cancer cells; • Molecular pathways, especially involving non-coding RNAs, regulate autophagy in prostate cancer; • Autophagy possesses both diagnostic and prognostic roles in prostate cancer, with promises for clinical application.

Background: The patient's position during the recovery time after arthroplasty surgery can be a factor in reducing complications and improving patients’ condition. Therefore, this study was performed to compare the knee range of motion after soft tissue repair in both flexion and extension positions of total knee arthroplasty. Methods: This study is a double-blind clinical trial. The study population was all candidates for total knee arthroplasty surgery in Al-Zahra and Kashani hospitals in Isfahan from July 2011 to September 2012. The sample size was selected using the statistical formula of 88 patients and randomly divided into two groups of flexion and extension. In the first group during the knee soft tissue repair, the knee was in flexion and in the second group it was in extension and then it was repaired. Information such as age, sex, body mass index and surgical position were recorded in the checklist. The knee range of motion was measured at the end of the first, second, fourth, eighth and twelfth weeks and recorded in a checklist. In order to compare the pattern of changes in mean knee range of motion over time in the two groups, mixed linear models and conventional marginal models to generalized estimator equations were used by STATA software. Results: The results showed that there was no significant difference between the flexion and extension groups in knee range of motion. In both groups, the mean knee range of motion increased with time (P

Introduction: ECG data play an important role in the diagnostics of various cardiovascular diseases. Classification of multi-lead ECG signals could be challenging even for well-trained physicians. In this study we propose a new approach for multi-lead ECG classification. Method: Five-types of 15-lead ECG data namely healthy control, bundle branch block, cardiomyopathy, Dysrhythmia, and myocardial infarction patients from two types of datasets, 5319 and 6647 heartbeats from Baqiyatallah and PTB Diagnostic ECG database, were used, respectively. One-dimensional total variation regularization was used to denoising ECG data. Heartbeats were extracted by one cardiologist and saved as images with jpg format. Histogram of oriented gradients method was used to extract feature of images. for classification task support vector machine and fully connected neural network were used. Five-fold cross validation was used for validating the models. Result: For 15-lead ECG PTB Diagnostic database, the best classification models are SVM model with cubic (accuracy: 99.9%, Range: 99.77% - 100%) and quadratic (accuracy: 99.88%, Range: 99.77%-100%) kernel function, for this dataset fully connected accuracy is 99.4% with range of 99.02%- 99.70%. Regarding to the Baqyatallah dataset SVM with cubic (accuracy: 99.83%, Range:99.72%-100%) and quadratic (accuracy: 99.77%, Range: 99.62%-99.9%) were the best classification model and the accuracy for fully connected neural network was 99.1% with the range of 98.59%-99.62% based on HOG descriptors. Expected sigmodal kernel all classification method have accuracy more than 99%. Discussion: simultaneous use of HOG feature extraction method and appropriate classification algorithm such as SVM or fully connected neural network can classify 15-lead ECG heart-beat for different heart disease with high accuracy and adding other relevant patients’ information can be easily done in order to increase the method performance.

Abstract Urological cancers are among the most common malignancies around the world. In particular, bladder cancer severely threatens human health due to its aggressive and heterogeneous nature. Various therapeutic modalities have been considered for the treatment of bladder cancer although its prognosis remains unfavorable. It is perceived that treatment of bladder cancer depends on an interdisciplinary approach combining biology and engineering. The nanotechnological approaches have been introduced in the treatment of various cancers, especially bladder cancer. The current review aims to emphasize and highlight possible applications of nanomedicine in eradication of bladder tumor. Nanoparticles can improve efficacy of drugs in bladder cancer therapy through elevating their bioavailability. The potential of genetic tools such as siRNA and miRNA in gene expression regulation can be boosted using nanostructures by facilitating their internalization and accumulation at tumor sites and cells. Nanoparticles can provide photodynamic and photothermal therapy for ROS overgeneration and hyperthermia, respectively, in the suppression of bladder cancer. Furthermore, remodeling of tumor microenvironment and infiltration of immune cells for the purpose of immunotherapy are achieved through cargo‐loaded nanocarriers. Nanocarriers are mainly internalized in bladder tumor cells by endocytosis, and proper design of smart nanoparticles such as pH‐, redox‐, and light‐responsive nanocarriers is of importance for targeted tumor therapy. Bladder cancer biomarkers can be detected using nanoparticles for timely diagnosis of patients. Based on their accumulation at the tumor site, they can be employed for tumor imaging. The clinical translation and challenges are also covered in current review.

Abstract Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS‐based nanoparticles (CS‐NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS‐NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P‐glycoprotein (P‐gp) to reverse drug resistance. These nanoarchitectures can provide co‐delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co‐loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid‐, carbon‐, polymeric‐ and metal‐based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS‐NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS‐NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH‐sensitive release of DOX can occur. Furthermore, redox‐ and light‐responsive CS‐NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS‐NPs, we expect to soon see significant progress towards clinical translation.

Abstracts 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

Background: Phenylketonuria (PKU) is a genetic autosomal recessive disorder, which, if not treated on time, can lead to mental retardation and severe developmental delay. The aim of this study was to assess the PKU neonatal screening program in Kerman County, Iran. Methods: This was a health system research study carried out on all newborns screened for PKU from 2012 to 2018 in Kerman. Data were extracted from the Comprehensive Social Genetics Program forms, genetic records, and the national form for investigation of genetic disease incidence. Results: Totally, 121,533 newborns were screened. 108,972 (89.7%) were Iranian, and 12,561 (10.3%) were non-Iranian. Screening coverage in the Iranian population was 92.1%. 80.9% of Iranian and 62.8% of non-Iranian newborns were screened from 3 to 5 days of age. Timely screening of newborns in the Iranian and non-Iranian populations in 2012 was 70.0% and 46.9%, and in 2018, it was 90.2% and 75.1%, respectively. The first visit at the PKU treatment center in 30.7% of Iranian and 33.3% of non-Iranian neonates was before 14 days of age. In the Iranian population residing in Kerman, the incidence rate of PKU was estimated to be 1.35 per 10,000 live births. 62.5% of parents of Iranian and 100% of parents of non-Iranian PKU patients were relatives. Conclusion: PKU screening coverage in Kerman is relatively acceptable, and most newborns were screened on time. Timely screening of newborns in both populations has increased since the beginning of the program until the time of this study. Interventions are required to improve early diagnosis and start treatment during the first 2 weeks of life. The incidence of PKU in Kerman County is approximately equal to the national average. Due to the fact that most parents of PKU patients are relatives, increasing awareness to prevent consanguineous marriages can be effective in decreasing the incidence of this disease.

ObjectiveThere is a limited understanding of the impact of the family-centered empowerment model (FCEM) on the psychological symptoms in post-myocardial infarction (MI). This study aimed to evaluate the effectiveness of the FCEM on the psychological improvement of patients with MI.MethodsThe present study was a randomized controlled trial (RCT) where patients experienced a standard home cardiac rehabilitation (CR) or CR utilizing the FCEM approach. The empowerment of patients was estimated during nine assessments, such as pre- and post-intervention. Factors, such as quality of life (QoL), state and trait anxiety, and perceived stress, were evaluated. A Bayesian multivariate mixed-effects model was used to simultaneously investigate the effect of the intervention group on study outcomes across the time.ResultsAmong all the participants in this study, 24 (34.3%) were women with a total mean ± standard deviation (SD) of 61.40 ± 12.83 and 24.87 ± 3.80 for age and body mass index (BMI). The participants who were in the FCEM group had a significantly higher mean level of perceived stress (β = 28.80), state anxiety (β = 16.20), trait anxiety (β = 3.65), physical (β = 38.54), and mental QoL (β = 42.14). Moreover, the individuals in the FCEM group had a significantly higher mean level of general health (β = 31.64) in the physical dimension of QoL, vitality (β = 15.04), mental role limitation (β = 21.84), and mental health (β = 18.16) in the mental dimension of QoL.ConclusionsThe FCEM can be a valuable treatment mechanism for patients with post-MI to improve their stress, anxiety, and QoL.

Background and Objectives: Investigating the changes in CT scans of patients is one of the most important methods to determine the prognosis of patients with head trauma, which has been considered by researchers. The aim of this study was to determine the findings of delayed CT scan in blunt head trauma patients referred to Shahid Bahonar Hospital of Kerman in 2020. Methods: This was a descriptive-analytical study. All patients with blunt head trauma underwent the initial Brain CT based on indications according to the guideline after six Hour of monitoring in the emergency room if they hadnchr(chr(chr('39')39chr('39'))39chr(chr('39')39chr('39')))t any discharge conditions based on the indications in the guideline The brain controls CT was performed. Findings were analyzed by SPSS25 software. Chi-square, Independent T test, ANOVA and logistic regression were used. Results: The results showed that 98.5% of the participants had no changes in their control CT scan. In the change group, 40% of cases had decreased hemorrhage, 35% of cases had increased hemorrhage and 25% of them had new intracranial hemorrhage. There was not also a statistically significant relationship between gender, drug history, outcome, initial CT-Scan findings, age, GCS score, systolic blood pressure, heart rate and duration with CT changes (in unchanged, exacerbated, recovered groups) (P> 0.05). But the results showed that the frequency of exacerbation of symptoms in people with underlying cranial disease was significantly higher than other groups (P=0.05). Conclusion: According to the results, it is possible that performing a primary CT scan in patients with head trauma in EDs is a good method for assessing the general condition of patients with mild to moderate trauma. However, evaluation of the necessity of control CT scan requires research with a larger sample size and longer follow-up.

Background & Objectives: The critical conditions of the epidemic covid-19 may have different effects on the rate of mortality of other people in the community. The aim of this study was to determine the evaluation of mortality trend before and after the onset of Corona crisis in Jahrom County, south of Iran. Methods: This descriptive study was performed by secondary data analysis death certificate during 2016-2020. The studied variables were collected based on a checklist from the data of the death registration system of the health center and also mortality statistics announced by the organization for civil registration. Results: In a total of 3785 deaths occurred during the study period, of which 2250 (59.5%) were in male and the rest were female. The average annual number of deaths before and after the Corona epidemic was 701 and 981, respectively. Cardiovascular disease, cerebral infarction, and cancer were the three leading causes of death before the onset of Corona crisis, respectively, and cardiovascular disease, Covid-19, and cerebrovascular disease were the most common causes of death after the onset of Corona crisis, respectively. After the Corona crisis, the cause of death from road accidents and cancer was reduced by 32.60% to 48.61% and the Influenza-like illness was increased by 110.25%. Conclusion: The average number of deaths occurred after the Corona epidemic has increased by 39% compared to before the epidemic. Cardiovascular diseases are the first and most common causes of death in Jahrom before and after the Corona epidemic.

Functional data are generally curves indexed over a time domain, and land-use regression (LUR) is a promising spatial technique for generating high-resolution spatial estimation of retrospective long-term air pollutants. We developed a methodology for the novel functional land-use regression (FLUR) model, which provides high-resolution spatial and temporal estimations of retrospective pollutants. Long-term fine particulate matter (PM2.5) in the megacity of Tehran, Iran, was used as the practical example. The hourly measured PM2.5 concentrations were averaged for each hour and in each air monitoring station. Penalized smoothing was employed to construct the smooth PM2.5 diurnal curve using averaged hourly data in each of the 30 stations. Functional principal component analysis (FPCA) was used to extract FPCA scores from pollutant curves, and LUR models were fitted on FPCA scores. The mean of all PM2.5 diurnal curves had a maximum of 39.58 µg/m3 at 00:26 a.m. and a minimum of 29.27 µg/m3 at 3:57 p.m. The FPCA explained about 99.5% of variations in the observed diurnal curves across the city using just three components. The evaluation of spatially predicted long-term PM2.5 diurnal curves every 15 min provided a series of 96 high-resolution exposure maps. The presented methodology and results could benefit future environmental epidemiological studies.

Objective: To review the prevalence of cryptosporidiosis among animal population of Iran. Methods: Data were systematically gathered from 1 January 2000 to 1 January 2020 in the Islamic Republic of Iran from the following electronic databases: PubMed, Springer, Google Scholar, Science Direct, Scopus, Web of Science, Magiran, and Scientific Information Database (SID). According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and inclusion criteria, 88 eligible studies were obtained. Results: The pooled prevalence of cryptosporidiosis using random and fixed effects model according to heterogeneity among animals was as follows: rodents 18.8% (95% CI 12.6%-25.0%), camels 17.1% (95% CI 8.6%-25.7%), cattle 16.8% (95% CI 13.4%-20.1%), goats 14.1% (95% CI 5.2%-23.0%), horses 12.2% (95% CI 8.3%- 16.2%), birds 10.5% (95% CI 7.6%-13.4%), sheep 9.9% (95% CI 2.4%-4.9%), cats 8.8% (95% CI 4.8%-12.8%) and dogs 3.7% (95% CI 7.0%-12.8%). Conclusions: Cryptosporidiosis has been reported and present in a wide range of animals in Iran over the years and has a high prevalence in most of these species.

Background: For decades, static stretching has been the standard benchmark for training programs, because it has been shown to increase flexibility compared with other methods of stretching. Objective: The current study investigated and compared the effects of active dynamic stretching and passive static stretching on hamstring tightness. Methods: For this experiment, 64 female students were enrolled and randomly assigned to active dynamic or passive static stretching groups (n = 32 each). The first and second experimental groups were trained with repetitive dynamic stretching and static stretching exercises, respectively. Exercises were performed 10 times per limb, 3 times per day, 5 days per week for 4 weeks. Hamstring muscle length measurements were repeated in weeks 2 and 4. Statistical analysis of the results was performed by t-test and repeated measures ANOVA using SPSS 15. Results: Both experimental groups showed significant improvements in the active knee extension range of motion during the intervention (P < 0.001). However, active stretching showed better results and had a greater effect on range of motion in comparison with static stretching.Conclusion: Active dynamic training can be considered a suitable method for increasing the flexibility of the hamstring muscle and, consequently, reducing the complications and problems associated with hamstring tightness.

Immune response, proliferation, migration and angiogenesis are juts a few of cellular events that are regulated by transforming growth factor-β (TGF-β) in cells. A number of studies have documented that TGF-β undergoes abnormal expression in different diseases, e.g., diabetes, cancer, fibrosis, asthma, arthritis, among others. This has led to great fascination into this signaling pathway and developing agents with modulatory impact on TGF-β. Curcumin, a natural-based compound, is obtained from rhizome and roots of turmeric plant. It has a number of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-diabetes and so on. Noteworthy, it has been demonstrated that curcumin affects different molecular signaling pathways such as Wnt/β-catenin, Nrf2, AMPK, mitogen-activated protein kinase and so on. In the present review, we evaluate the potential of curcumin in regulation of TGF-β signaling pathway to corelate it with therapeutic impacts of curcumin. By modulation of TGF-β (both upregulation and down-regulation), curcumin ameliorates fibrosis, neurological disorders, liver disease, diabetes and asthma. Besides, curcumin targets TGF-β signaling pathway which is capable of suppressing proliferation of tumor cells and invading cancer cells.

Pancreatic cancer (PC) is one of the leading causes of death and is the fourth most malignant tumor in men. The epigenetic and genetic alterations appear to be responsible for development of PC. Small interfering RNA (siRNA) is a powerful genetic tool that can bind to its target and reduce expression level of a specific gene. The various critical genes involved in PC progression can be effectively targeted using diverse siRNAs. Moreover, siRNAs can enhance efficacy of chemotherapy and radiotherapy in inhibiting PC progression. However, siRNAs suffer from different off target effects and their degradation by enzymes in serum can diminish their potential in gene silencing. Loading siRNAs on nanoparticles can effectively protect them against degradation and can inhibit off target actions by facilitating targeted delivery. This can lead to enhanced efficacy of siRNAs in PC therapy. Moreover, different kinds of nanoparticles such as polymeric nanoparticles, lipid nanoparticles and metal nanostructures have been applied for optimal delivery of siRNAs that are discussed in this article. This review also reveals that how naked siRNAs and their delivery systems can be exploited in treatment of PC and as siRNAs are currently being applied in clinical trials, significant progress can be made by translating the current findings into the clinical settings.

The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.

MicroRNAs (miRNAs) are well-known regulators of biological mechanisms with a small size of 19–24 nucleotides and a single-stranded structure. miRNA dysregulation occurs in cancer progression. miRNAs can function as tumor-suppressing or tumor-promoting factors in cancer via regulating molecular pathways. Breast and lung cancers are two malignant thoracic tumors in which the abnormal expression of miRNAs plays a significant role in their development. Phosphatase and tensin homolog (PTEN) is a tumor-suppressor factor that is capable of suppressing the growth, viability, and metastasis of cancer cells via downregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling. PTEN downregulation occurs in lung and breast cancers to promote PI3K/Akt expression, leading to uncontrolled proliferation, metastasis, and their resistance to chemotherapy and radiotherapy. miRNAs as upstream mediators of PTEN can dually induce/inhibit PTEN signaling in affecting the malignant behavior of lung and breast cancer cells. Furthermore, long non-coding RNAs and circular RNAs can regulate the miRNA/PTEN axis in lung and breast cancer cells. It seems that anti-tumor compounds such as baicalein, propofol, and curcumin can induce PTEN upregulation by affecting miRNAs in suppressing breast and lung cancer progression. These topics are discussed in the current review with a focus on molecular pathways.

Doxorubicin (DOX) is extensively applied in cancer therapy due to its efficacy in suppressing cancer progression and inducing apoptosis. After its discovery, this chemotherapeutic agent has been frequently used for cancer therapy, leading to chemoresistance. Due to dose-dependent toxicity, high concentrations of DOX cannot be administered to cancer patients. Therefore, experiments have been directed towards revealing underlying mechanisms responsible for DOX resistance and ameliorating its adverse effects. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is activated to increase levels of reactive oxygen species (ROS) in cells to protect them against oxidative stress. It has been reported that Nrf2 activation is associated with drug resistance. In cells exposed to DOX, stimulation of Nrf2 signaling protects cells against cell death. Various upstream mediators regulate Nrf2 in DOX resistance. Strategies, both pharmacological and genetic interventions, have been applied for reversing DOX resistance. However, Nrf2 induction is of importance for alleviating side effects of DOX. Pharmacological agents with naturally occurring compounds as the most common have been used for inducing Nrf2 signaling in DOX amelioration. Furthermore, signaling networks in which Nrf2 is a key player for protection against DOX adverse effects have been revealed and are discussed in the current review.

Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

Prostate cancer (PCa) accounts for a high number of deaths in males with no available curative treatments. Patients with PCa are commonly diagnosed in advanced stages due to the lack of symptoms in the early stages. Recently, the research focus was directed toward gene editing in cancer therapy. Small interfering RNA (siRNA) intervention is considered as a powerful tool for gene silencing (knockdown), enabling the suppression of oncogene factors in cancer. This strategy is applied to the treatment of various cancers including PCa. The siRNA can inhibit proliferation and invasion of PCa cells and is able to promote the anti-tumor activity of chemotherapeutic agents. However, the off-target effects of siRNA therapy remarkably reduce its efficacy in PCa therapy. To date, various carriers were designed to improve the delivery of siRNA and, among them, nanoparticles are of importance. Nanoparticles enable the targeted delivery of siRNAs and enhance their potential in the downregulation of target genes of interest. Additionally, nanoparticles can provide a platform for the co-delivery of siRNAs and anti-tumor drugs, resulting in decreased growth and migration of PCa cells. The efficacy, specificity, and delivery of siRNAs are comprehensively discussed in this review to direct further studies toward using siRNAs and their nanoscale-delivery systems in PCa therapy and perhaps other cancer types.

Bladder cancer (BC) is the 11th most common diagnosed cancer, and a number of factors including environmental and genetic ones participate in BC development. Metastasis of BC cells into neighboring and distant tissues significantly reduces overall survival of patients with this life-threatening disorder. Recently, studies have focused on revealing molecular pathways involved in metastasis of BC cells, and in this review, we focus on microRNAs (miRNAs) and their regulatory effect on epithelial-to-mesenchymal transition (EMT) mechanisms that can regulate metastasis. EMT is a vital process for migration of BC cells, and inhibition of this mechanism restricts invasion of BC cells. MiRNAs are endogenous non-coding RNAs with 19–24 nucleotides capable of regulating different cellular events, and EMT is one of them. In BC cells, miRNAs are able to both induce and/or inhibit EMT. For regulation of EMT, miRNAs affect different molecular pathways such as transforming growth factor-beta (TGF-β), Snail, Slug, ZEB1/2, CD44, NSBP1, which are, discussed in detail this review. Besides, miRNA/EMT axis can also be regulated by upstream mediators such as lncRNAs, circRNAs and targeted by diverse anti-tumor agents. These topics are also discussed here to reveal diverse molecular pathways involved in migration of BC cells and strategies to target them to develop effective therapeutics.

Cancer is one of the life-threatening disorders that, in spite of excellent advances in medicine and technology, there is no effective cure for. Surgery, chemotherapy, and radiotherapy are extensively applied in cancer therapy, but their efficacy in eradication of cancer cells, suppressing metastasis, and improving overall survival of patients is low. This is due to uncontrolled proliferation of cancer cells and their high migratory ability. Finding molecular pathways involved in malignant behavior of cancer cells can pave the road to effective cancer therapy. In the present review, we focus on phosphatase and tensin homolog (PTEN) signaling as a tumor-suppressor molecular pathway in gastric cancer (GC). PTEN inhibits the PI3K/Akt pathway from interfering with the migration and growth of GC cells. Its activation leads to better survival of patients with GC. Different upstream mediators of PTEN in GC have been identified that can regulate PTEN in suppressing growth and invasion of GC cells, such as microRNAs, long non-coding RNAs, and circular RNAs. It seems that antitumor agents enhance the expression of PTEN in overcoming GC. This review focuses on aforementioned topics to provide a new insight into involvement of PTEN and its downstream and upstream mediators in GC. This will direct further studies for evaluation of novel signaling networks and their targeting for suppressing GC progression.

Resveratrol (Res) is a well-known natural product that can exhibit important pharmacological activities such as antioxidant, anti-diabetes, anti-tumor, and anti-inflammatory. An evaluation of its therapeutic effects demonstrates that this naturally occurring bioactive compound can target different molecular pathways to exert its pharmacological actions. Transforming growth factor-beta (TGF-β) is an important molecular pathway that is capable of regulating different cellular mechanisms such as proliferation, migration, and angiogenesis. TGF-β has been reported to be involved in the development of disorders such as diabetes, cancer, inflammatory disorders, fibrosis, cardiovascular disorders, etc. In the present review, the relationship between Res and TGF-β has been investigated. It was noticed that Res can inhibit TGF-β to suppress the proliferation and migration of cancer cells. In addition, Res can improve fibrosis by reducing inflammation via promoting TGF-β down-regulation. Res has been reported to be also beneficial in the amelioration of diabetic complications via targeting the TGF-β signaling pathway. These topics are discussed in detail in this review to shed light on the protective effects of Res mediated via the modulation of TGF-β signaling.

Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of epithelial-mesenchymal transition (EMT) mechanism, therefore reducing metastasis. Additionally, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression.

Molecular signaling pathways play a significant role in the regulation of biological mechanisms, and their abnormal expression can provide the conditions for cancer development. The signal transducer and activator of transcription 3 (STAT3) is a key member of the STAT proteins and its oncogene role in cancer has been shown. STAT3 is able to promote the proliferation and invasion of cancer cells and induces chemoresistance. Different downstream targets of STAT3 have been identified in cancer and it has also been shown that microRNA (miR), long non-coding RNA (lncRNA) and other molecular pathways are able to function as upstream mediators of STAT3 in cancer. In the present review, we focus on the role and regulation of STAT3 in gastric cancer (GC). miRs and lncRNAs are considered as potential upstream mediators of STAT3 and they are able to affect STAT3 expression in exerting their oncogene or onco-suppressor role in GC cells. Anti-tumor compounds suppress the STAT3 signaling pathway to restrict the proliferation and malignant behavior of GC cells. Other molecular pathways, such as sirtuin, stathmin and so on, can act as upstream mediators of STAT3 in GC. Notably, the components of the tumor microenvironment that are capable of targeting STAT3 in GC, such as fibroblasts and macrophages, are discussed in this review. Finally, we demonstrate that STAT3 can target oncogene factors to enhance the proliferation and metastasis of GC cells.