Melatonin: An important anticancer agent in colorectal cancer.

Colorectal cancer is one of the most common cancers among the elderly, which is also seen in the forms of hereditary syndromes occurring in younger individuals. Numerous studies have been conducted to understand the molecular and cellular pathobiology underlying colorectal cancer. These studies have found that cellular signaling pathways are at the core of colorectal cancer pathology. Because of this, new agents have been proposed as possible candidates to accompany routine therapy regimens. One of these agents is melatonin, a neuro-hormone known best for its essential role in upholding the circadian rhythm and orchestrating the many physiologic changes it accompanies. Melatonin is shown to be able to modulate many signaling pathways involved in many essential cell functions, which if deregulated cause an accelerated pace towards cancer. More so, melatonin is involved in the regulation of immune function, tumor microenvironment, and acts as an antioxidant agent. Many studies have focused on the beneficial effects of melatonin in colorectal cancers, such as induction of apoptosis, increased sensitivity to chemotherapy agents and radiotherapy, limiting cellular proliferation, migration, and invasion. The present review aims to illustrate the known significance of melatonin in colorectal cancer and to address possible clinical use.

Combination of exercise training and L-arginine reverses aging process through suppression of oxidative stress, inflammation, and apoptosis in the rat heart.

Aging-induced progressive decline of molecular and metabolic factors in the myocardium is suggested to be related with heart dysfunction and cardiovascular disease. Therefore, we evaluated the effects of exercise training and L-arginine supplementation on oxidative stress, inflammation, and apoptosis in ventricle of the aging rat heart. Twenty-four 24-month-aged Wistar rats were randomly divided into four groups: the aged control, aged exercise, aged L-arginine (orally administered with 150 mg/kg for 12 weeks), and aged exercise + L-arginine groups. Six 4-month-old rats were also considered the young control. Animals with training program performed exercise on a treadmill 5 days/week for 12 weeks. After 12 weeks, protein levels of Bax, Bcl-2, pro-caspase-3/cleaved caspase-3, cytochrome C, and heat shock protein (HSP)-70 were assessed. Tissue contents of total anti-oxidant capacity, superoxide dismutase, catalase, and levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6 were analyzed. Histological and fibrotic changes were also evaluated. Treadmill exercise and L-arginine supplementation significantly alleviated aging-induced apoptosis with enhancing HSP-70 expression, increasing anti-oxidant enzyme activity, and suppressing inflammatory markers in the cardiac myocytes. Potent attenuation in apoptosis, inflammation, and oxidative stress was indicated in the rats with the combination of L-arginine supplementation and exercise program in comparison with each group (p < 0.05). In addition, fibrosis percentage and collagen accumulation were significantly lower in the rats with the combination treatment of L-arginine and exercise (p < 0.05). Treadmill exercise and L-arginine supplementation provided protection against age-induced increase in the myocyte loss and formation of fibrosis in the ventricle through potent suppression of oxidative stress, inflammations, and apoptosis pathways.

Combination of quercetin and exercise training attenuates depression in rats with 1,2-dimethylhydrazine-induced colorectal cancer: Possible involvement of inflammation and BDNF signalling.

NEW FINDINGS: What is the central question of this study? What are the alleviative effects of the combination of exercise training and quercetin supplementation on colorectal cancer-related depression in rats with 1,2-dimethylhydrazine-induced colorectal cancer and what is the corresponding signalling pathway? What is the main finding and its importance? We showed that the combination of exercise training and quercetin supplementation resulted in a significant decrease in tumour incidence and improvement in depressive-like behaviours through modulation of the BDNF/TrKß/ß-catenin axis in the prefrontal cortex. ABSTRACT: In addition to physical problems, depression is considered to be one of the most important challenges for patients with various types of cancers, particularly colorectal cancer. Inflammation and upregulation of brain neurotrophic factors are two major links between cancer and depression. In this study, we aimed to evaluate the alleviative effects of quercetin and exercise training on depressive-like behaviours in rats with 1,2-dimethylhydrazine (DMH)-induced colorectal cancer and to investigate the underlying mechanisms. Animals were assigned into the following five groups: (i) control group; (ii) DMH (20 mg kg-1 s.c., once a week for 10 weeks); (iii) DMH for 10 weeks, followed by quercetin (50 mg kg-1 p.o., once per week) for 12 weeks; (iv) DMH for 10 weeks, followed by exercise training for 12 weeks; and (v) DMH for 10 weeks, followed by quercetin and exercise training for 12 weeks. The DMH-treated rats showed an increase in depressive-like behaviours in both open field and forced swimming tests. Histopathological examination revealed neural damage and reduced Nissl bodies in the prefrontal cortex. In addition, administration of DMH increased inflammatory cytokines in the serum, prefrontal cortex and tumour tissues and decreased the expression levels of brain-derived neurotrophic factor (BDNF), tyrosine kinase ß receptor (TrKß) and ß-catenin in the cortex. In contrast, treatment with quercetin and exercise training effectively alleviated all the above-mentioned DMH-associated behavioural, biochemical and histopathological alterations without changing its anti-tumour activity. Taken together, our results show that the combination of quercetin and exercise training exerts potent anti-tumour and anti-depressive effects through suppression of inflammation and upregulation of the BDNF/TrKß/ß-catenin axis in the prefrontal cortex.

The modulatory effects of exercise on the inflammatory and apoptotic markers in rats with 1,2-dimethylhydrazine-induced colorectal cancer.

This study aimed to investigate the underlying mechanisms in anti-tumorigenesis effects of exercise through evaluation of inflammation and apoptosis. Twenty-four Wistar rats were divided into control, exercise, 1,2-dimethylhydrazine (DMH), and DMH + exercise. After a week, rats in the DMH group were given DMH twice a week for 2 weeks. Animals in the exercise groups performed exercise on a treadmill 5 days/week for 8 weeks. After 8 weeks of training, levels of COX-2, PCNA, Bax, Bcl-2, and procaspase-3/cleaved caspase-3 were assessed. Histological changes, number of aberrant crypt foci (ACF), and serum levels of TNF-α and IL-6 were also analyzed. ACF number was significantly decreased following the exercise program. Protein levels of COX-2 and PCNA and serum levels of IL-6 and TNF-α were significantly elevated in the rats receiving DMH and downregulated after performing the exercise program (P < 0.05). Exercise upregulated apoptosis, which was evident from the increased Bax/Bcl2 ratio, and enhanced the expression levels of activated caspase-3 as compared to the DMH group. The colonic architecture was improved in DMH + exercise. Exercise can effectively attenuate DMH-induced increase of inflammatory markers. Exercise induces apoptosis at the downstream of the inflammatory response. Therefore, exercise may play a role as a moderator of inflammation to exert protective effects against colon cancer.

Melatonin-mediated regulation of autophagy: Making sense of double-edged sword in cancer.

Much research has been conducted to discover novel techniques to reverse the process of tumorigenesis and, cure already stablished malignancies. One well-stablished approach has been the use of organic compounds and naturally found agents such as melatonin whose anticancer effects have been shown in multiple studies, signaling a unique opportunity regarding cancer prevention and treatment. Various agents use a variety of methods to exert their anticancer effects. Two of the most important of these methods are interfering with cell signaling pathways and changing cellular functions, such as autophagy, which is essential in maintaining cellular stability against multiple exogenous and endogenous sources of stress, and is a major tool to evade early cell death. In this study, the importance of melatonin and autophagy are discussed, and the effects of melatonin on autophagy, and its contribution in the process of tumorigenesis are then noted.

Overexpression of tensin homolog deleted on chromosome ten (PTEN) by ciglitazone sensitizes doxorubicin-resistance leukemia cancer cells to treatment.

Overcoming multidrug resistance (MDR) is a final goal of various recent studies, in which combination of different compounds and conventional chemotherapeutics results in circumventing MDR and hence cancer progression. Therefore, we aimed to investigate the effects of peroxisome proliferator-activated receptors (PPARs)-γ on MDR in doxorubicin-resistant human myelogenous leukemia cells. The effect of doxorubicin on cell viability following treatment with ciglitazone was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The activity of P-glycoprotein (P-gp), as one of the membrane transporters, was determined by the rhodamine 123 (Rho 123) assay. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used for the measurement of P-gp, and tensin homolog deleted on chromosome ten (PTEN) expression at mRNA and protein, respectively. For evaluation of doxorubicin (DOX)-induced apoptosis by annexin V/PI staining was used. Ciglitazone significantly increases the cytotoxic effects of DOX. In addition, ciglitazone considerably decreased the expression levels and activity of P-gp in DOX-resistant K562 cells. Furthermore, upon the ciglitazone treatment, PTEN expression could be increased in K562/DOX cells in a PPARγ-dependent manner. Moreover, ciglitazone significantly enhanced DOX-induced apoptosis in K562/DOX cells. The combination treatment of K562/DOX leukemia cancer cells with doxorubicin and ciglitazone might be an effective strategy in inducing apoptosis and reversing developed MDR, and more importantly decreasing the adverse side effects of these agents.

Quercetin: A functional dietary flavonoid with potential chemo-preventive properties in colorectal cancer.

Recently, an intense attention has been paid to the application of natural compounds as a novel therapeutic strategy for cancer treatment. Quercetin, a natural flavonol present in many commonly consumed food items, is widely demonstrated to exert inhibitory effects on cancer progression through various mechanisms. Since there is a strong association with diets containing abundant vegetables, fruits, and grains, and significant decline in the risk of colon cancer, accumulation studies have focused on the anticancer potential of quercetin in colorectal cancer. Cell cycle arrest, increase in apoptosis, antioxidant replication, modulation of estrogen receptors, regulation of signaling pathways, inhibition of and metastasis and angiogenesis are among various mechanisms underlying the chemo-preventive effects of quercetin in colorectal cancer. This review covers various therapeutic interactions of Quercetin as to how targets cellular involved in cancer treatment.

Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go.

Chronic primary orofacial pain (OFP) conditions such as painful temporomandibular disorders (pTMDs; i.e., myofascial pain and arthralgia), idiopathic trigeminal neuralgia (TN), and burning mouth syndrome (BMS) are seemingly idiopathic, but evidence support complex and multifactorial etiology and pathophysiology. Important fragments of this complex array of factors have been identified over the years largely with the help of preclinical studies. However, findings have yet to translate into better pain care for chronic OFP patients. The need to develop preclinical assays that better simulate the etiology, pathophysiology, and clinical symptoms of OFP patients and to assess OFP measures consistent with their clinical symptoms is a challenge that needs to be overcome to support this translation process. In this review, we describe rodent assays and OFP pain measures that can be used in support of chronic primary OFP research, in specific pTMDs, TN, and BMS. We discuss their suitability and limitations considering the current knowledge of the etiology and pathophysiology of these conditions and suggest possible future directions. Our goal is to foster the development of innovative animal models with greater translatability and potential to lead to better care for patients living with chronic primary OFP.

SIRT1: a promising therapeutic target in type 2 diabetes mellitus.

A significant increase in the worldwide incidence and prevalence of type 2 diabetic mellitus (T2DM) has elevated the need for studies on novel and effective therapeutic strategies. Sirtuin 1 (SIRT1) is an NAD + dependent protein deacetylase with a critical function in the regulation of glucose/lipid metabolism, insulin resistance, inflammation, oxidative stress, and mitochondrial function. SIRT1 is also involved in the regulation of insulin secretion from pancreatic ß-cells and protecting these cells from inflammation and oxidative stress-mediated tissue damages. In this regard, major SIRT1 activators have been demonstrated to exert a beneficial impact in reversing T2DM-related complications including cardiomyopathy, nephropathy, retinopathy, and neuropathy, hence treating T2DM. Therefore, an accumulating number of recent studies have investigated the efficacy of targeting SIRT1 as a therapeutic strategy in T2DM. In this review we aimed to discuss the current understanding of the physiological and biological roles of SIRT1, then its implication in the pathogenesis of T2DM, and the therapeutic potential of SIRT1 in combating T2DM.

Melatonin increases 5-flurouracil-mediated apoptosis of colorectal cancer cells through enhancing oxidative stress and downregulating survivin and XIAP.

Introduction: Colorectal cancer (CRC) is one of the most lethal human malignancies with a global alarming rate of incidence. The development of resistance against common chemotherapeutics such as 5-fluorouracil (5-FU) remains a big burden for CRC therapy. Therefore, we investigated the effects of melatonin on the increasing 5-FU- mediated apoptosis and its underlying mechanism in SW-480 CRC cell line. Methods: The effects of melatonin and 5- FU, alone or in combination, on cell proliferation were evaluated using an MTT assay. Further, Annexin-V Flow cytometry was used for determining the effects of melatonin and 5-FU on the apoptosis of SW-480 cell lines. The expression levels of Bax, Bcl-2, pro-caspase-3/activated caspase 3, X-linked inhibitor of apoptosis proteins (XIAP), and survivin were measured after 48 hours incubation with drugs. Cellular levels of reactive oxygen species (ROS), catalase, superoxide dismutase and glutathione peroxidase were also evaluated. Results: Melatonin and 5-FU significantly decreased the cell proliferation of SW-480 cells. Combination of 5-FU with melatonin significantly decreased the IC50 value of 5-FU from 100 µM to 50 µM. Moreover, combination therapy increased intracellular levels of ROS and suppressed antioxidant enzymatic activities (P < 0.05). Treatment with either melatonin or 5-FU resulted in the induction of apoptosis in comparison to control (P > 0.05). XIAP and survivin expression levels potently decreased after combination treatment with melatonin and 5-FU (P < 0.05). Conclusion: We demonstrated that melatonin exerts a reversing effect on the resistance to apoptosis by targeting oxidative stress, XIAP and survivin in CRC cells. Therefore, more studies need for better understanding of underlying mechanisms for beneficial effects of combination of melatonin and 5-FU.

Parasympathetic, but not sympathetic denervation, suppressed colorectal cancer progression.

Disruption in the nerve-tumor interaction is now considered as a possible anticancer strategy for treating various cancer types, particularly colorectal cancer. However, the underlying mechanisms are not still fully understood. Therefore, the present study aimed to evaluate the effects of sympathetic and parasympathetic denervation on the inhibition of colorectal cancer progression in early and late phases and assess the involvement of nerve growth factor in denervation mediated anticancer effects. One-hundred and fifty male Wistar rats were assigned into 15 groups. Seven groups comprising the control group, 1,2-dimethylhydrazine (DMH) group, sympathetic denervation group (celiac-mesenteric ganglionectomy and guanethidine sulphate administration), parasympathetic denervation group (vagotomy and atropine administration), and combination group were used in the early-stage protocol. For the late-stage protocol, eight groups comprising the control, DMH, surgical and pharmacological sympathetic and parasympathetic denervation groups, combination group, and 5-flourouracil group were considered. After 8 weeks, sympathetic and parasympathetic denervation significantly reduced ACF numbers in rats receiving DMH. On the other hand, in the late stages, parasympathetic but not sympathetic denervation resulted in significant reductions in tumor incidence, tumor volume and weight, cell proliferation (indicated by reduced immunostaining of PCNA and ki-67), and angiogenesis (indicated by reduced immunostaining of CD31 and VEGF expression levels), and downregulated NGF, ß2 adrenergic, and M3 receptors. It can be concluded that parasympathetic denervation may be of high importance in colon carcinogenesis and suggested as a possible therapeutic modality in late stages of colorectal cancer.

Involvement of IGF/IGFBP/Erk axis in the exercise-mediated preventive effects on colorectal cancer in rats.

Recent studies have indicated that downregulation of insulin-like growth factor (IGF)-1 and its downstream targets are the main mechanisms underlying the anti-cancer impact of exercise. Therefore, we examined the impact of exercise on chemically induced-aberrant crypt foci (ACF), the earliest step of colorectal carcinogenesis, in rats and involvement of the IGF-1/IGF binding protein (IGFBP)-3/Erk axis. Twenty-four male Wistar rats were assigned into two groups (n=12): the control and exercise group. After eight weeks of training intervention, 6 rats were randomly selected from each group and received four injections of 1,2-dimethylhydrazine (DMH; 40 mg/kg), for two weeks. 0.2% methylene blue staining was used to evaluate the number of ACF in the colon. IGF-1 and IGFBP-3 protein levels in the serum were measured using commercially available ELISA kits for rat. The expression levels of proliferating cell nuclear antigen (PCNA), Erk1/2 and p-Erk1/2 were evaluated in colon tissue. Histological assessments were also performed in all groups. We found that the total number of ACF was significantly lowered after eight-week exercise (P<0.05). Moreover, the exercise program downregulated the IGF-1, PCNA, and p-Erk1/2 expressions and upregulated IGFBP-3 expression. Exercise was also found to increase the goblet cell number and improved colon architecture. Our finding demonstrated reduced ACF number in rat colons following exercise training, and this function may be associated with the inhibition of IGF-1/IGFBP-3/Erk1/2 signaling. Therefore, exercise appears to result in a lower number of ACF for preventing colon cancer.

Doxorubicin loaded magnetism nanoparticles based on cyclodextrin dendritic-graphene oxide inhibited MCF-7 cell proliferation.

Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a formulation based on graphene oxide as an anticancer drug delivery system for DOX in MCF-7 breast cancer cells, to address these issues. In vitro release studies confirmed that the synthesized formulation has an improved release profile in acidic conditions (similar to the tumor microenvironment). Further in vitro studies, including MTT, uptake, and apoptosis assays were performed. The toxic effects of the nanocarrier on the kidney, heart and liver of healthy rats were also evaluated. We observed that the DOX-loaded carrier improved the cytotoxic effect of DOX on the breast cell line compared to free DOX. In summary, our results introduce the DOX-loaded carrier as a potential platform for in vitro targeting of cancer cells and suggest further studies are necessary to investigate its in vivo anti-cancer potential.

In vitro and in vivo anticancer effects of syringic acid on colorectal cancer: Possible mechanistic view.

This study aimed to evaluate the in vitro effects of syringic acid on human colorectal cancer cells (SW-480) and the effect of orally administered syringic acid on in vivo models of colorectal cancer induced in rats by administration of 1,2-dimethylhydrazine (DMH). In vitro effects of syringic acid treatment on human colorectal cancer SW-480 cell lines were assessed by performing cell proliferation assay (MTT and Trypan Blue staining), apoptosis assays (TUNEL assay, Annexin-V/PI flowcytometry and lactate dehydrogenase release assay), measuring reactive oxygen species (ROS), antioxidant enzymes and DNA damage, and evaluating protein levels of proliferative genes, and autophagy markers. In vitro anti-cancer roles of syringic acid were studied in rats with DMH-induced colorectal cancer cells. The effect of orally administered syringic acid (50 mg/kg) on tumor growth and incidence was studied in four groups (n = 6) of animals injected with DMH and treated for 15 weeks. Syringic acid treatment resulted in a significant dose-dependent inhibition of cellular proliferation, induction of apoptosis through increasing cellular ROS and DNA damage levels, as well as downregulating major proliferative genes. In vivo, treatment of rats with syringic acid demonstrated a statistically significant tumor volume and incidence reduction when compared to the control. This is the first study demonstrating an in vivo growth inhibitory effect of orally administered syringic acid on colorectal tumors in rats.

DNA damage response and breast cancer development: Possible therapeutic applications of ATR, ATM, PARP, BRCA1 inhibition.

Breast cancer is the most common and significant cancers in females regarding the loss of life quality. Similar to other cancers, one of the etiologic factors in breast cancer is DNA damage. A plethora of molecules are responsible for sensing DNA damage and mediating actions which lead to DNA repair, senescence, cell cycle arrest and if damage is unbearable to apoptosis. In each of these, aberrations leading to unrepaired damage was resulted in uncontrolled proliferation and cancer. Another cellular function is autophagy defined as a process eliminating of unnecessary proteins in stress cases involved in pathogenesis of cancer. Knowing their role in cancer, scholars have tried to develop strategies in order to target DDR and autophagy. Further, the interactions of DDR and autophagy plus their regulatory role on each other have been focused simultaneously. The present review study has aimed to illustrate the importance of DDR and autophagy in breast cancer according to the related studies and uncover the relation between DDR and autophagy and its significance in breast cancer therapy.

Quercetin attenuated oxidative DNA damage through NRF2 signaling pathway in rats with DMH induced colon carcinogenesis.

Accumulating recent studies have demonstrated the preventive and therapeutic effects of polyphonic compounds such as quercetin in colorectal cancer. Therefore, we aimed to evaluate the underlying mechanisms for positive effects of quercetin in rats with 1,2-dimethylhydrazine (DMH)- induced colorectal cancer. For this purpose, male Wistar rats were classified as 6 groups, including group 1 without any intervention, group 2 as quercetin received rats (50 mg/kg), groups 3 as DMH received rats (20 mg/kg) group 4-6 DMH and quercetin received rats. DNA damage, DNA repair, the expression levels and activities of enzymic antioxidants, non-enzymic antioxidants, and NRF2/Keap1 signaling were evaluated in colon tissues of all groups. Our results showed significant suppression of DNA damage and induction of DNA repair in DMH + Quercetin groups, particularly in entire-period in comparison to other groups (p < .05). The expression levels and activities of enzymic and non-enzymic antioxidants were increased in DMH + Quercetin groups (p < .05). Lipid and protein peroxidation were significantly suppressed in DMH + Quercetin groups (p < .05). In addition, quercetin also modulated NRF2/Keap1 signaling and its targets, detoxifying enzymes in DMH + Quercetin groups. Our finding demonstrated that quercetin supplementation effectively reversed DMH-mediated oxidative stress and DNA damage through targeting NRF2/Keap1 signaling pathway.

The Response of Ventral Tegmental Area Dopaminergic Neurons to Bupropion: Excitation or Inhibition?

INTRODUCTION: Antidepressants can modulate brain monoamines by acting on pre-synaptic and postsynaptic receptors. Autoreceptors can reduce the monoamines effect on the somatodendritic or pre-synaptic regions despite its postsynaptic counter effects. The direct effect of some antidepressants is related to its temporal and spatial bioavailability in the vicinity of these receptors (still a matter of controversies). This research evaluated the direct effect of acute bupropion on the Ventral Tegmental Area (VTA) dopaminergic neuronal firing rate. METHODS: Male Wistar rats were divided into intracerebroventricular and microiontophoretic groups with 14 subgroups (n=5 in each subgroup). Amounts of 1, 0.5, 0.1, 0.01, 0.001, and 0.0001 mol of bupropion (5 µL/3 min) were microinfused to the first group and then the ejected amounts of bupropion at -500, -300, -150, -50 nA of electrical currents (1 mol, pH=4.5, 5 min) were applied to the second group. The control and sham subgroups were studied in each group, too. The units with stable firing rates were extracted, and the effect of bupropion was evaluated statistically with a P value less than 0.05 as the level of significance. RESULTS: The highest amount of bupropion in the intracerebroventricular application could excite 42% of the neurons and inhibit 56% of them, but the highest amount of microiontophoretic application of bupropion could inhibit 97.5% of the neurons. The neuronal response to bupropion was dose-dependent in all treated groups. CONCLUSION: The dual effects of intracerebroventricular bupropion on the VTA dopaminergic neurons but solo inhibitory effect of its microiontophoretic application reflect the intra-VTA and extra-VTA heterogenic cellular and molecular control over the dopaminergic outflow that can be mediated by different receptors. The dopamine autoreceptors on the VTA dopaminergic neurons have complex modulatory effects on the dopaminergic response.

DNA damage response and repair in ovarian cancer: Potential targets for therapeutic strategies.

Ovarian cancer is among the most lethal gynecologic malignancies with a poor survival prognosis. The current therapeutic strategies involve surgery and chemotherapy. Research is now focused on novel agents especially those targeting DNA damage response (DDR) pathways. Understanding the DDR process in ovarian cancer necessitates having a detailed knowledge on a series of signaling mediators at the cellular and molecular levels. The complexity of the DDR process in ovarian cancer and how this process works in metastatic conditions is comprehensively reviewed. For evaluating the efficacy of therapeutic agents targeting DNA damage in ovarian cancer, we will discuss the components of this system including DDR sensors, DDR transducers, DDR mediators, and DDR effectors. The constituent pathways include DNA repair machinery, cell cycle checkpoints, and apoptotic pathways. We also will assess the potential of active mediators involved in the DDR process such as therapeutic and prognostic candidates that may facilitate future studies.

Exosomes: natural nanoparticles as bio shuttles for RNAi delivery.

Application of exosomes, natural nanoscale vesicles, as specific delivery vehicles has received considerable attention in recent past years. The presence of various adhesive proteins on the surface of these lipid bilayers, gives them the ability to interact with cellular membranes. Although the function of exosomes was not known for some time, further researches have suggested that they are effective in multiple cellular pathways, as well as pathogenesis of a broad range of diseases including neurodegenerative diseases, cardiovascular diseases, and more importantly, multiple human malignancies. As erstwhile research brought to light more aspects of exosomes' biogenesis and functions, researchers sought to benefit from their effects in therapeutic and diagnostic purposes. Gene therapy is one of these fields that has seen many endeavors made. The present review article looks at gene therapy and its latest advancements, structure and function of exosomes and their role as bio shuttles in various clinical contexts relating to gene therapy.