Advances and challenges of the cell-based therapies among diabetic patients.

Diabetes mellitus is a significant global public health challenge, with a rising prevalence and associated morbidity and mortality. Cell therapy has evolved over time and holds great potential in diabetes treatment. In the present review, we discussed the recent progresses in cell-based therapies for diabetes that provides an overview of islet and stem cell transplantation technologies used in clinical settings, highlighting their strengths and limitations. We also discussed immunomodulatory strategies employed in cell therapies. Therefore, this review highlights key progresses that pave the way to design transformative treatments to improve the life quality among diabetic patients.

PI3K/AKT pathway as a pivotal regulator of epithelial-mesenchymal transition in lung tumor cells.

Lung cancer, as the leading cause of cancer related deaths, is one of the main global health challenges. Despite various progresses in diagnostic and therapeutic methods, there is still a high rate of mortality among lung cancer patients, which can be related to the lack of clinical symptoms to differentiate lung cancer from the other chronic respiratory disorders in the early tumor stages. Most lung cancer patients are identified in advanced and metastatic tumor stages, which is associated with a poor prognosis. Therefore, it is necessary to investigate the molecular mechanisms involved in lung tumor progression and metastasis in order to introduce early diagnostic markers as well as therapeutic targets. Epithelial-mesenchymal transition (EMT) is considered as one of the main cellular mechanisms involved in lung tumor metastasis, during which tumor cells gain the metastatic ability by acquiring mesenchymal characteristics. Since, majority of the oncogenic signaling pathways exert their role in tumor cell invasion by inducing the EMT process, in the present review we discussed the role of PI3K/AKT signaling pathway in regulation of EMT process during lung tumor metastasis. It has been reported that the PI3K/AKT acts as an inducer of EMT process through the activation of EMT-specific transcription factors in lung tumor cells. MicroRNAs also exerted their inhibitory effects during EMT process by inhibition of PI3K/AKT pathway. This review can be an effective step towards introducing the PI3K/AKT pathway as a suitable therapeutic target to inhibit the EMT process and tumor metastasis in lung cancer patients.

Integrins as the pivotal regulators of cisplatin response in tumor cells.

Cisplatin (CDDP) is a widely used first-line chemotherapeutic drug in various cancers. However, CDDP resistance is frequently observed in cancer patients. Therefore, it is required to evaluate the molecular mechanisms associated with CDDP resistance to improve prognosis among cancer patients. Integrins are critical factors involved in tumor metastasis that regulate cell-matrix and cell-cell interactions. They modulate several cellular mechanisms including proliferation, invasion, angiogenesis, polarity, and chemo resistance. Modification of integrin expression levels can be associated with both tumor progression and inhibition. Integrins are also involved in drug resistance of various solid tumors through modulation of the tumor cell interactions with interstitial matrix and extracellular matrix (ECM). Therefore, in the present review we discussed the role of integrin protein family in regulation of CDDP response in tumor cells. It has been reported that integrins mainly promoted the CDDP resistance through interaction with PI3K/AKT, MAPK, and WNT signaling pathways. They also regulated the CDDP mediated apoptosis in tumor cells. This review paves the way to suggest the integrins as the reliable therapeutic targets to improve CDDP response in tumor cells.

Effect of resveratrol and curcumin and the potential synergism on hypertension: A mini-review of human and animal model studies.

Resveratrol (RES) and curcumin (CUR) are two of the most extensively studied bioactive compounds in cardiovascular research from the past until today. These compounds have effectively lowered blood pressure by downregulating the renin-angiotensin system, exerting antioxidant effects, and exhibiting antiproliferative activities on blood vessels. This study aims to summarize the results of human and animal studies investigating the effects of CUR, RES, and their combination on hypertension and the molecular mechanisms involved. The published trials' results are controversial regarding blood pressure reduction with different doses of RES and CUR, highlighting the need to address this issue.

Long non-coding RNAs as the critical regulators of PI3K/AKT, TGF-ß, and MAPK signaling pathways during breast tumor progression.

Breast cancer (BC) as one of the most common causes of human deaths among women, is always considered one of the global health challenges. Despite various advances in diagnostic and therapeutic methods, a significant percentage of BC patients have a poor prognosis due to the lack of therapeutic response. Therefore, investigating the molecular mechanisms involved in BC progression can improve the therapeutic and diagnostic strategies in these patients. Cytokine and growth factor-dependent signaling pathways play a key role during BC progression. In addition to cytokines and growth factors, long non-coding RNAs (lncRNAs) have also important roles in regulation of such signaling pathways. Therefore, in the present review we discussed the role of lncRNAs in regulation of PI3K/AKT, MAPK, and TGF-ß signaling pathways in breast tumor cells. It has been shown that lncRNAs mainly have an oncogenic role through the promotion of these signaling pathways in BC. This review can be an effective step in introducing the lncRNAs inhibition as a probable therapeutic strategy to reduce tumor growth by suppression of PI3K/AKT, MAPK, and TGF-ß signaling pathways in BC patients. In addition, considering the oncogenic role and increased levels of lncRNAs expressions in majority of the breast tumors, lncRNAs can be also considered as the reliable diagnostic markers in BC patients.

MicroRNAs as the pivotal regulators of cisplatin resistance in head and neck cancers.

Although, there is a high rate of good prognosis in early stage head and neck tumors, about half of these tumors are detected in advanced stages with poor prognosis. A combination of chemotherapy, radiotherapy, and surgery is the treatment option in head and neck cancer (HNC) patients. Although, cisplatin (CDDP) as the first-line drug has a significant role in the treatment of HNC patients, CDDP resistance can be observed in a large number of these patients. Therefore, identification of the molecular mechanisms involved in CDDP resistance can help to reduce the side effects and also provides a better therapeutic management. MicroRNAs (miRNAs) as the post-transcriptional regulators play an important role in drug resistance. Therefore, in the present review we investigated the role of miRNAs in CDDP response of head and neck tumors. It has been reported that the miRNAs exerted their roles in CDDP response by regulation of signaling pathways such as WNT, NOTCH, PI3K/AKT, TGF-ß, and NF-kB as well as apoptosis, autophagy, and EMT process. The present review paves the way to suggest a non-invasive miRNA based panel marker for the prediction of CDDP response among HNC patients. Therefore, such diagnostic miRNA based panel marker reduces the CDDP side effects and improves the clinical outcomes of these patients following an efficient therapeutic management.

MicroRNAs as the critical regulators of autophagy-mediated cisplatin response in tumor cells.

Chemotherapy is one of the most common therapeutic methods in advanced and metastatic tumors. Cisplatin (CDDP) is considered as one of the main first-line chemotherapy drugs in solid tumors. However, there is a high rate of CDDP resistance in cancer patients. Multi-drug resistance (MDR) as one of the main therapeutic challenges in cancer patients is associated with various cellular processes such as drug efflux, DNA repair, and autophagy. Autophagy is a cellular mechanism that protects the tumor cells toward the chemotherapeutic drugs. Therefore, autophagy regulatory factors can increase or decrease the chemotherapy response in tumor cells. MicroRNAs (miRNAs) have a pivotal role in regulation of autophagy in normal and tumor cells. Therefore, in the present review, we discussed the role of miRNAs in CDDP response through the regulation of autophagy. It has been reported that miRNAs mainly increased the CDDP sensitivity in tumor cells by inhibition of autophagy. PI3K/AKT signaling pathway and autophagy-related genes (ATGs) were the main targets of miRNAs in the regulation of autophagy-mediated CDDP response in tumor cells. This review can be an effective step to introduce the miRNAs as efficient therapeutic options to increase autophagy-mediated CDDP sensitivity in tumor cells.

Role of the long non-coding RNAs in regulation of Gemcitabine response in tumor cells.

Chemotherapy is widely used as one of the first line therapeutic methods in cancer patients. However, chemotherapeutic resistance is one of the most common problems in cancer patients, which leads to the therapeutic failure and tumor relapse. Considering the side effects of chemotherapy drugs in normal tissues, it is required to investigate the molecular mechanisms involved in drug resistance to improve the therapeutic strategies in cancer patients. Long non-coding RNAs (lncRNAs) have pivotal roles in regulation of cellular processes associated with drug resistance. LncRNAs deregulations have been frequently reported in a wide range of chemo-resistant tumors. Gemcitabine (GEM) as a nucleoside analog has a wide therapeutic application in different cancers. However, GEM resistance is considered as a therapeutic challenge. Considering the role of lncRNAs in the occurrence of GEM resistance, in the present review we discussed the molecular mechanisms of lncRNAs in regulation of GEM response among cancer patients. It has been reported that lncRNAs have mainly an oncogenic role as the inducers of GEM resistance through direct or indirect regulation of transcription factors, autophagy, polycomb complex, and signaling pathways such as PI3K/AKT, MAPK, WNT, JAK/STAT, and TGF-ß. This review paves the way to present the lncRNAs as non-invasive markers to predict GEM response in cancer patients. Therefore, lncRNAs can be introduced as the efficient markers to reduce the possible chemotherapeutic side effects in GEM resistant cancer patients and define a suitable therapeutic strategy among these patients.

PRC2 mediated KLF2 down regulation: a therapeutic and diagnostic axis during tumor progression.

Surgery and chemo-radiotherapy are used as the common first-line treatment options in many cancers. However, tumor relapse is observed in many cancer patients following such first-line treatments. Therefore, targeted therapy according to the molecular cancer biology can be very important in reducing tumor recurrence. In this regard, a wide range of monoclonal antibodies against the growth factors and their receptors can offer more targeted treatment in cancer patients. However, due to the importance of growth factors in the normal biology of body cells, side effects can also be observed following the application of growth factor inhibitors. Therefore, more specific factors should be introduced as therapeutic targets with less side effects. Krüppel-like factors 2 (KLF2) belongs to the KLF family of transcription factors that are involved in the regulation of many cellular processes. KLF2 deregulations have been also reported during the progression of many tumors. In the present review we discussed the molecular mechanisms of KLF2 during tumor growth and invasion. It has been shown that the KLF2 as a tumor suppressor is mainly inhibited by the non-coding RNAs (ncRNAs) through the polycomb repressive complex 2 (PRC2) recruitment. This review is an effective step towards introducing the KLF2 as a suitable diagnostic and therapeutic target in cancer patients.

Molecular mechanisms of microRNA-216a during tumor progression.

MicroRNAs (miRNAs) as the members of non-coding RNAs family are involved in post-transcriptional regulation by translational inhibiting or mRNA degradation. They have a critical role in regulation of cell proliferation and migration. MiRNAs aberrations have been reported in various cancers. Considering the importance of these factors in regulation of cellular processes and their high stability in body fluids, these factors can be suggested as suitable non-invasive markers for the cancer diagnosis. MiR-216a deregulation has been frequently reported in different cancers. Therefore, in the present review we discussed the molecular mechanisms of the miR-216a during tumor progression. It has been reported that miR-216a mainly functioned as a tumor suppressor through the regulation of signaling pathways and transcription factors. This review paves the way to suggest the miR-216a as a probable therapeutic and diagnostic target in cancer patients.

Single-nucleotide polymorphisms as important risk factors of diabetes among Middle East population.

Diabetes is a chronic metabolic disorder that leads to the dysfunction of various tissues and organs, including eyes, kidneys, and cardiovascular system. According to the World Health Organization, diabetes prevalence is 8.8% globally among whom about 90% of cases are type 2 diabetes. There are not any significant clinical manifestations in the primary stages of diabetes. Therefore, screening can be an efficient way to reduce the diabetic complications. Over the recent decades, the prevalence of diabetes has increased alarmingly among the Middle East population, which has imposed exorbitant costs on the health care system in this region. Given that the genetic changes are among the important risk factors associated with predisposing people to diabetes, we examined the role of single-nucleotide polymorphisms (SNPs) in the pathogenesis of diabetes among Middle East population. In the present review, we assessed the molecular pathology of diabetes in the Middle East population that paves the way for introducing an efficient SNP-based diagnostic panel for diabetes screening among the Middle East population. Since, the Middle East has a population of 370 million people; the current review can be a reliable model for the introduction of SNP-based diagnostic panels in other populations and countries around the world.

PI3K/AKT signaling pathway as a critical regulator of epithelial-mesenchymal transition in colorectal tumor cells.

Colorectal cancer (CRC) is one of the most frequent gastrointestinal malignancies that are considered as a global health challenge. Despite many progresses in therapeutic methods, there is still a high rate of mortality rate among CRC patients that is associated with poor prognosis and distant metastasis. Therefore, investigating the molecular mechanisms involved in CRC metastasis can improve the prognosis. Epithelial-mesenchymal transition (EMT) process is considered as one of the main molecular mechanisms involved in CRC metastasis, which can be regulated by various signaling pathways. PI3K/AKT signaling pathway has a key role in CRC cell proliferation and migration. In the present review, we discussed the role of PI3K/AKT pathway CRC metastasis through the regulation of the EMT process. It has been shown that PI3K/AKT pathway can induce the EMT process by down regulation of epithelial markers, while up regulation of mesenchymal markers and EMT-specific transcription factors that promote CRC metastasis. This review can be an effective step toward introducing the PI3K/AKT/EMT axis to predict prognosis as well as a therapeutic target among CRC patients. Video Abstract.

Applications of poly(lactic acid) in bone tissue engineering: A review article.

BACKGROUND: Bone tissue engineering is a promising approach to large-scale bone regeneration. This involves the use of an artificial extracellular matrix or scaffold and osteoblasts to promote osteogenesis and ossification at defect sites. Scaffolds are constructed using biomaterials that typically have properties similar to those of natural bone. METHOD: In this study, which is a review of the literature, various evidences have been discussed in the field of Poly Lactic acid (PLA) polymer application and modifications made on it in order to induce osteogenesis and repair bone lesions. RESULTS: PLA is a synthetic aliphatic polymer that has been extensively used for scaffold construction in bone tissue engineering owing to its good processability, biocompatibility, and flexibility in design. However, PLA has some drawbacks, including low osteoconductivity, low cellular adhesion, and the possibility of inflammatory reactions owing to acidic discharge in a living environment. To overcome these issues, a combination of PLA and other biomaterials has been introduced. CONCLUSIONS: This short review discusses PLA's characteristics of PLA, its applications in bone regeneration, and its combination with other biomaterials.

Cell cycle related long non-coding RNAs as the critical regulators of breast cancer progression and metastasis.

Cell cycle is one of the main cellular mechanisms involved in tumor progression. Almost all of the active molecular pathways in tumor cells directly or indirectly target the cell cycle progression. Therefore, it is necessary to assess the molecular mechanisms involved in cell cycle regulation in tumor cells. Since, early diagnosis has pivotal role in better cancer management and treatment, it is required to introduce the non-invasive diagnostic markers. Long non-coding RNAs (LncRNAs) have higher stability in body fluids in comparison with mRNAs. Therefore, they can be used as efficient non-invasive markers for the early detection of breast cancer (BCa). In the present review we have summarized all of the reported lncRNAs involved in cell cycle regulation in BCa. It has been reported that lncRNAs mainly affect the cell cycle in G1/S transition through the CCND1/CDK4-6 complex. Present review paves the way of introducing the cell cycle related lncRNAs as efficient markers for the early detection of BCa.

MicroRNAs as the Critical Regulators of Forkhead Box Protein Family in Pancreatic, Thyroid, and Liver Cancers.

The metabolism of human body is mainly regulated by the pancreas, liver, and thyroid using the hormones or exocrine secretions that affect the metabolic processes from food digestion to intracellular metabolism. Therefore, metabolic organ disorders have wide clinical symptoms that severely affect the quality of patient's life. The pancreatic, liver, and thyroid cancers as the main malignancies of the metabolic system have always been considered as one of the serious health challenges worldwide. Despite the novel therapeutic modalities, there are still significant high mortality and recurrence rates, especially in liver and pancreatic cancer patients which are mainly related to the late diagnosis. Therefore, it is required to assess the molecular bases of tumor progressions to introduce novel early detection and therapeutic markers in these malignancies. Forkhead box (FOX) protein family is a group of transcription factors that have pivotal roles in regulation of cell proliferation, migration, and apoptosis. They function as oncogene or tumor suppressor during tumor progression. MicroRNAs (miRNAs) are also involved in regulation of cellular processes. Therefore, in the present review, we discussed the role of miRNAs during pancreatic, thyroid, and liver tumor progressions through FOX regulation. It has been shown that miRNAs were mainly involved in tumor progression via FOXM and FOXO targeting. This review paves the way for the introduction of miR/FOX axis as an efficient early detection marker and therapeutic target in pancreatic, thyroid, and liver tumors.

Elucidated tumorigenic role of MAML1 and TWIST1 in gastric cancer is associated with Helicobacter pylori infection.

BACKGROUND: Epithelial-mesenchymal transition (EMT) has a fundamental role in tumor initiation, progression, and metastasis. Helicobacter pylori (HP) induces EMT and thus causes gastric cancer (GC) by deregulating multiple signaling pathways involved in EMT. TWIST1 and MAML1 have been confirmed to be critical inducers of EMT via diverse signaling pathways such as Notch signaling. This study aimed to investigate for the first time possible associations between TWIST1/MAML1 mRNA expression levels, HP infection, and clinicopathological characteristics in GC patients. METHOD: TWIST1 and MAML1 mRNA expression levels were evaluated in tumoral and adjacent normal tissues in 73 GC patients using the quantitative reverse transcription PCR (RT-qPCR) method. PCR technique was also applied to examine the infection with HP in GC samples. RESULTS: Upregulation of TWIST1 and MAML1 expression was observed in 35 (48%) and 34 (46.6%) of 73 tumor samples, respectively. Co-overexpression of these genes was found in 26 of 73 (35.6%) tumor samples; meanwhile, there was a significant positive correlation between MAML1 and TWIST1 mRNA expression levels (P < 0.001). MAML1 overexpression exhibited meaningful associations with advanced tumor stages (P = 0.006) and nodal metastases (P ˂ 0.001). 34 of 73 (46.6%) tumors tested positive for HP, and meanwhile, MAML1 expression was positively related with T (P = 0.05) and grade (P = 0.0001) in these HP-positive samples. Increased TWIST1 expression was correlated with patient sex (P = 0.035) and advanced tumor grade (P = 0.017) in HP-infected tumors. Furthermore, TWIST1 and MAML1 expression levels were inversely linked with histologic grade in HP-negative tumor samples (P = 0.021 and P = 0.048, respectively). CONCLUSION: We propose TWIST1 and MAML1 as potential biomarkers of advanced-stage GC that determine the characteristics and aggressiveness of the disease. Based on accumulating evidence and our findings, they can be introduced as promising therapeutic targets to modify functional abnormalities in cells that promote GC progression. Moreover, HP may enhance GC growth and metastasis by disrupting TWIS1/MAML1 expression patterns and related pathways.

Long non-coding RNAs as the critical regulators of epithelial mesenchymal transition in colorectal tumor cells: an overview.

Colorectal cancer (CRC) is the second most common cause of cancer mortality and a major health challenge worldwide. Despite advances in therapeutic and diagnostic methods, there is still a poor prognosis in CRC patients. Tumor recurrence and metastasis are the main causes of high mortality rate in these patients, which are due to late diagnosis in advanced tumor stages. Epithelial-mesenchymal transition (EMT) is known to be the most important cause of CRC metastasis, during which tumor cells obtain metastasis ability by losing epithelial features and gaining mesenchymal features. Long non-coding RNAs (lncRNAs) are pivotal regulators of EMT process. Regarding the higher stability of lncRNAs compared with coding RNAs in body fluids, they can be used as non-invasive diagnostic markers for EMT process. In the present review, we summarized all of the lncRNAs involved in regulation of EMT process during CRC progression and metastasis. It was observed that lncRNAs mainly induced the EMT process in CRC cells by regulation of EMT-related transcription factors, Poly comb repressive complex (PRC), and also signaling pathways such as WNT, NOTCH, MAPK, and Hippo.

Genetic and molecular biology of autism spectrum disorder among Middle East population: a review.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disease, characterized by impaired social communication, executive dysfunction, and abnormal perceptual processing. It is more frequent among males. All of these clinical manifestations are associated with atypical neural development. Various genetic and environmental risk factors are involved in the etiology of autism. Genetic assessment is essential for the early detection and intervention which can improve social communications and reduce abnormal behaviors. Although, there is a noticeable ASD incidence in Middle East countries, there is still a lack of knowledge about the genetic and molecular biology of ASD among this population to introduce efficient diagnostic and prognostic methods. MAIN BODY: In the present review, we have summarized all of the genes which have been associated with ASD progression among Middle East population. We have also categorized the reported genes based on their cell and molecular functions. CONCLUSIONS: This review clarifies the genetic and molecular biology of ASD among Middle East population and paves the way of introducing an efficient population based panel of genetic markers for the early detection and management of ASD in Middle East countries.

MicroRNAs as the critical regulators of tyrosine kinase inhibitors resistance in lung tumor cells.

Lung cancer is the second most common and the leading cause of cancer related deaths globally. Tyrosine Kinase Inhibitors (TKIs) are among the common therapeutic strategies in lung cancer patients, however the treatment process fails in a wide range of patients due to TKIs resistance. Given that the use of anti-cancer drugs can always have side effects on normal tissues, predicting the TKI responses can provide an efficient therapeutic strategy. Therefore, it is required to clarify the molecular mechanisms of TKIs resistance in lung cancer patients. MicroRNAs (miRNAs) are involved in regulation of various pathophysiological cellular processes. In the present review, we discussed the miRNAs that have been associated with TKIs responses in lung cancer. MiRNAs mainly exert their role on TKIs response through regulation of Tyrosine Kinase Receptors (TKRs) and down-stream signaling pathways. This review paves the way for introducing a panel of miRNAs for the prediction of TKIs responses in lung cancer patients. Video Abstract.

MicroRNAs as the critical regulators of Doxorubicin resistance in breast tumor cells.

BACKGROUND: Chemotherapy is one of the most common treatment options for breast cancer (BC) patients. However, about half of the BC patients are chemotherapeutic resistant. Doxorubicin (DOX) is considered as one of the first line drugs in the treatment of BC patients whose function is negatively affected by multi drug resistance. Due to the severe side effects of DOX, it is very important to diagnose the DOX resistant BC patients. Therefore, assessment of molecular mechanisms involved in DOX resistance can improve the clinical outcomes in BC patients by introducing the novel therapeutic and diagnostic molecular markers. MicroRNAs (miRNAs) as members of the non-coding RNAs family have pivotal roles in various cellular processes including cell proliferation and apoptosis. Therefore, aberrant miRNAs functions and expressions can be associated with tumor progression, metastasis, and drug resistance. Moreover, due to miRNAs stability in body fluids, they can be considered as non-invasive diagnostic markers for the DOX response in BC patients. MAIN BODY: In the present review, we have summarized all of the miRNAs that have been reported to be associated with DOX resistance in BC for the first time in the world. CONCLUSIONS: Since, DOX has severe side effects; it is required to distinguish the non DOX-responders from responders to improve the clinical outcomes of BC patients. This review highlights the miRNAs as pivotal regulators of DOX resistance in breast tumor cells. Moreover, the present review paves the way of introducing a non-invasive panel of prediction markers for DOX response among BC patients.