Recent advances in mesenchymal stem/stromal cells (MSCs)-based approaches for osteoarthritis (OA) therapy.

Recently, mesenchymal stem/stromal cells (MSCs) transplantation has been introduced as a promising option to support cartilage structure and improve its function in preclinical models and patients suffering from osteoarthritis (OA). MSCs strongly provoke their preferred influence in vivo by inhibiting the inflammatory responses and applying immunomodulation by releasing anti-inflammatory mediators such as transforming growth factor-ß and interleukin-10. Such mediators downregulate fibroblast-like synoviocytes growth and migration, leading to chondroprotection. Furthermore, improving the chondrocyte proliferation and extracellular matrix hemostasis in addition to the suppression of the matrix metalloproteinases activities can support cartilage tissue organization. In this light, various published results have demonstrated that MSCs therapy can considerably decrease pain and restore knee function in OA patients. In the current review, we have concentrated on recent advances in MSCs-based therapeutics to elicit both chondrogenic and chondroprotective impacts in OA patients, focusing on the last decade in vivo results.

Parental morphine exposure enhances morphine (but not methamphetamine) preference and increases monoamine oxidase-B level in the nucleus accumbens.

Opioid addiction is one of the most crucial issues in the world. Opioid abuse by parents makes children more prone to many psychological disorders such as drug addiction. Therefore, this study was carried out to examine the effect of morphine exposure 10 days before gestation on morphine and methamphetamine preference in male offspring. Adult Wistar rats (male and female) received morphine orally for 21 days and were drug free for 10 days. Thereafter, they were allowed to mate with either a morphine-abstinent or drug-naive rat. The male offspring were tested for morphine and methamphetamine preference with a three-bottle choice test. Moreover, the rewarding effects of morphine and methamphetamine were evaluated using a conditioned place preference test. To determine the mechanisms underlying these changes, monoamine oxidase-B (MAO-B) level was measured in the nucleus accumbens (NAC). Offspring of morphine-abstinent mothers and offspring of both-abstinent parents were found to consume morphine more than those of other groups, but in the case of methamphetamine, there were no differences. In addition, the offspring of morphine-abstinent parent(s) did not condition with a high dose of morphine in the conditioned place preference test. Administration of methamphetamine induced conditioning at different doses in controls and offspring of one or two morphine-abstinent parent(s), and there were no effects of parental morphine exposure on the dose of methamphetamine that was required for conditioning. Moreover, the level of MAO-B was increased in the NAC of offspring of morphine-abstinent parents as compared with the control group. These results demonstrate that offspring of a morphine-abstinent mother and a drug-naive father and offspring of two morphine-abstinent parents were more susceptible to opioid but not methamphetamine addiction. Moreover, parental morphine consumption did not have any effect on the reinforcing effect of methamphetamine in their offspring but induced morphine tolerance in the offspring. Although the level of MAO-B was elevated in the NAC, this did not correlate with the methamphetamine preference in offspring.

NMDA receptor subunits change in the prefrontal cortex of pure-opioid and multi-drug abusers: a post-mortem study.

Addiction is a chronic relapsing disorder and is one of the most important issues in the world. Changing the level of neurotransmitters and the activities of their receptors, play a major role in the pathophysiology of substance abuse disorders. It is well-established that N-methyl-D-aspartate receptors (NMDARs) play a significant role in the molecular basis of addiction. NMDAR has two obligatory GluN1 and two regionally localized GluN2 subunits. This study investigated changes in the protein level of GluN1, GluN2A, and GluN2B in the prefrontal cortex of drug abusers. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), and orbitofrontal cortex (OFC) were dissected from the brain of 101 drug addicts brains and were compared with the brains of non-addicts (N = 13). Western blotting technique was used to show the alteration in NMDAR subunits level. Data obtained using Western blotting technique showed a significant increase in the level of GluN1 and GluN2B, but not in GluN2A subunits in all the three regions (mPFC, lPFC, and OFC) of men whom suffered from addiction as compared to the appropriate controls. These findings showed a novel role for GluN1, GluN2B subunits, rather than the GluN2A subunit of NMDARs, in the pathophysiology of addiction and suggested their role in the drug-induced plasticity of NMDARs.

Perifosine enhances bevacizumab-induced apoptosis and therapeutic efficacy by targeting PI3K/AKT pathway in a glioblastoma heterotopic model.

Bevacizumab (BVZ) as an antiangiogenesis therapy leads to a transient therapeutic efficacy in high-grade glioma. However, the proapoptotic potential of BVZ has not been well elucidated, yet. There is also a tumor resistance to BVZ that is linked to post-treatment metalloproteinases and AKT activities. Herein, the association between therapeutic efficacy and putative proapoptotic activity of low-dose BVZ either alone or in combination with a specific inhibitor of AKT called perifosine (PRF), in a glioma model was investigated. BALB/c mice bearing C6 glioma tumor were treated with BVZ and PRF either alone or combined for 13 days (n = 11/group). At the end of treatments, apoptosis, proliferation and vascular density, in the xenografts (3/group) were detected by TUNEL staining, Ki67 and CD31 markers, respectively. Relative levels of cleaved-caspase3, phospho-AKT (Ser473) and matrix metalloproteinase2 (MMP2) were measured using western blotting. PRF and BVZ separately slowed down tumor growth along with the cell apoptosis induction associated with a profound increase in caspase3 activity through an AKT inhibition-related pathway for PRF but not BVZ. Unlike PRF, BVZ significantly increased the intratumor MMP2 and phospho-AKT (Ser473) levels coupled with the slight antiproliferative and significant antivascular effects. Co-administration of PRF and BVZ versus monotherapies potentiated the proapoptotic effects and reversed the BVZ-induced upregulation of phospho-AKT (Ser473) and MMP2 levels in C6 xenografts, leading to the optimal antiproliferative activity and tumor growth regression and longer survival. In conclusion, BVZ plus PRF renders a paramount proapoptotic effect, leading to a major therapeutic efficacy and might be a new substitute for GBM therapy in the clinic.

Evaluation of plasma sphingosine 1-phosphate, hepcidin and cardiovascular damage biomarkers (cardiac troponin I and homocysteine) in rats infected with brucellosis and vaccinated (Rev-1, RB-51).

Brucellosis is known as one of important zoonosis. Studying the histological and biochemical effects of the disease could help to increase our knowledge about it. The aim of the present study was to evaluate changes of plasma parameters after intraperitoneal injection of two species of Brucella (Brucella melitensis and Brucella abortus) and two vaccines (Rev-1, RB-51) in the rat. Forty male rats were divided into five groups (n = 8 in each group). Two groups received suspensions of Brucella abortus and Brucella melitensis and two other groups were injected intraperitoneally with two mentioned vaccines and the last group received only distilled water. The results showed a significant increase in sphingosine 1-phosphate, Malondialdehyde, hepcidin, homocysteine, cardiac troponin I and copper levels and a considerable decrease in the levels of iron and zinc (P ≤ 0.01) in infected groups compared to the control animals. In vaccinated groups, hepcidin was increased but other parameters were not changed in comparison to the control group. It can be concluded that increase of homocysteine and cardiac troponin I in brucellosis could be a warning for cardiac adverse effects. Besides, increase of sphingosine 1-phosphate probably indicates its stimulant and modulatory effects in anti- Brucellosis biochemical pathways of the host.

mRNA expression of dopamine receptors in peripheral blood lymphocytes of computer game addicts.

Excessive playing of computer games like some other behaviors could lead to addiction. Addictive behaviors may induce their reinforcing effects through stimulation of the brain dopaminergic mesolimbic pathway. The status of dopamine receptors in the brain may be parallel to their homologous receptors in peripheral blood lymphocytes (PBLs). Here, we have investigated the mRNA expression of dopamine D3, D4 and D5 receptors in PBLs of computer game addicts (n = 20) in comparison to normal subjects (n = 20), using a real-time PCR method. The results showed that the expression level of D3 and D4 dopamine receptors in computer game addicts were not statistically different from the control group. However, the expression of the mRNA of D5 dopamine receptor was significantly down-regulated in PBLs of computer game addicts and reached 0.42 the amount of the control group. It is concluded that unlike with drug addiction, the expression levels of the D3 and D4 dopamine receptors in computer game addicts are not altered compared to the control group. However, reduced level of the D5 dopamine receptor in computer game addicts may serve as a peripheral marker in studies where the confounding effects of abused drugs are unwanted.

Early-onset Alzheimer's disease in two Iranian families: a genetic study.

BACKGROUND: Early-onset Alzheimer's disease (EOAD) represents less than 5% of all AD cases. Autosomal dominant EOAD has been defined as the occurrence of at least three cases in three generations. Mutations in the amyloid precursor protein (APP), presenilin-1 and presenilin-2 genes have been recognized to be the cause of EOAD. OBJECTIVE: We investigated the genotype of EOAD in two generations of two families with EOAD living in an Iranian village. METHODS: The polymerase chain reaction method was used to study the presenilin-1 and APP genes in 25 subjects of these generations. RESULTS: A guanine-to-adenine transition in exon 17 of the APP gene resulting in a valine-to-isoleucine substitution at codon 717 was detected in 14 subjects including 6 patients with EOAD. CONCLUSION: This mutation demonstrates the importance of γ-secretase, the necessity of early detection of patients with memory decline in the susceptible population and raising public awareness of consanguinity marriages.

The effect of morphine administration on GluN3B NMDA receptor subunit mRNA expression in rat brain.

Opioid addiction is critically dependent on the activation of N­methyl­D­aspartate (NMDA) receptors, which are widely found in the mesocorticolimbic system. Meanwhile, opioid addiction may affect the expression level of NMDA receptor subunits. The existence of GluN3 subunits in the NMDA receptor's tetramer structure reduces the excitatory current of the receptor channel. We evaluated the changes in the mRNA expression pattern of the GluN3B subunit of the NMDA receptor in rat brains following acute and chronic exposure to morphine. Chronic, escalating intraperitoneal doses of morphine or saline were administered twice daily to male Wistar rats for six days. Two other groups were injected with a single acute dose of morphine or saline. The mRNA level of the GluN3B subunit of the NMDA receptor in the striatum, hippocampus, and nucleus accumbens (NAc) was measured by real­time PCR. mRNA expression of the GluN3B subunit was considerably augmented (3.15 fold) in the NAc of animals chronically treated with morphine compared to the control group. The difference between rats that were chronically administered morphine and control rats was not statistically significant for other evaluated brain areas. In rats acutely treated with morphine, no significant differences were found for GluN3B subunit expression in the examined brain regions compared to the control group. It was concluded that chronic exposure to morphine notably increased the GluN3B subunit of the NMDA receptor in NAc. The extent of the impact of this finding on opioid addiction and its features requires further evaluation in future studies.

Autophagy genes and signaling pathways in endometrial decidualization and pregnancy complications.

Autophagy is a process that occurs in almost all eukaryotic cells and this process is controlled by several molecular processes. Its biological roles include the provision of energy, the maintenance of cell homeostasis, and the promotion of aberrant cell death. The importance of autophagy in pregnancy is gradually becoming recognized. In literature, it has been indicated that autophagy has three different effects on the onset and maintenance of pregnancy: embryo (embryonic development), feto-maternal immune crosstalk, and maternal (decidualization). In humans, proper decidualization is a major predictor of pregnancy accomplishment and it can be influenced by different factors. This review highlights the genes, pathways, regulation, and function of autophagy in endometrial decidualization and other involved factors in this process.

The Effectiveness of Universal Educational Interventions for Prevention of Illicit Drug Use among University Students: A Systematic Review.

Background: The extent of illicit drug use among university students necessitates effective preventive programs. To identify and assess the effectiveness of university-based interventions in preventing or reducing illicit drug use. Methods: The MEDLINE (PubMed), SCOPUS, ISI (Web of Science), and other sources were searched according to the Cochrane Collaboration method. RCTs, CRTs and non- RCTs evaluating university-based interventions designed to prevent illicit drug use were reviewed. Data were extracted independently by two reviewers. The quality of the publications was assessed. Interventions were classified by type, provider, duration, and theoretical background. Results: Of 6652 papers, 11 studies met the eligibility criteria that were conducted between 1987 and 2020. The effectiveness of interventions was different. Substantial heterogeneity among the studies prevented the integration of results for estimating summaries. Conclusion: Despite the importance of the subject, there is a paucity of studies about specific educational programs for illicit drug use, indicating the necessity of further research in other countries.

The effect of tiagabine on physical development and neurological reflexes and their relationship with the γ-aminobutyric acid switch in the rat cerebral cortex during developmental stages.

In the present study, we focused on γ-aminobutyric acid (GABA) signaling through the γ-aminobutyric acid transporter (GAT) in the developing rat cerebral cortex. Tiagabine was used as a GAT inhibitor. The offspring received injections from birth until postnatal day 21 intraperitoneally. Physical development and neurological reflexes were assessed daily. Tiagabine did not influence body weight, the onset and completion of incisor eruption, or the time to appearance of cliff avoidance. However, the onset and completion of eye opening, ear unfolding, and fur growth occurred earlier in treated pups. Further, the slanted board test and righting reflex showed accelerated development (i.e. decreased time to criterion) when compared with the control group. To determine whether the obtained effects are related to the GABA switch, we examined the protein and mRNA expression of the K(+)-Cl(-) cotransporter KCC2 using western blotting and RT-PCR, respectively. Downregulation of KCC2 mRNA and protein levels was observed when GAT was inhibited. The results may indicate a role of GAT in the neurobehavioral changes that accompany the developmental switch in GABA function.

Pre-mating administration of theophylline could prevent the transgenerational effects of maternal morphine dependence on offspring anxiety behavior: The role of dopamine receptors.

Opioid addiction causes some molecular alterations in the brain reward pathway, such as changes in gene expression that may be transferred to the next generation via epigenetic mechanisms such as histone acetylation. This study aimed to evaluate the effect of theophylline as an HDAC (Histone deacetylases) activator on D1 and D2 dopamine receptor expression in the nucleus accumbens (NAc) and anxiety behavior in the offspring of morphine-dependent female rats. Female rats were exposed to escalating doses of morphine for six days and were then treated with theophylline (20 mg/kg) or saline for 10 days before mating with normal male rats. Male and female offspring were tested for anxiety behavior using an elevated plus maze apparatus. Besides, the expression of D1 and D2 dopamine receptors in the NAc was evaluated by real-time PCR (polymerase chain reaction). Results showed that offspring of morphine-dependent female rats had increased expression of both D1 and D2 receptors in the NAc, as well as decreased anxiety behavior, compared to control offspring. However, the mentioned effects were returned to normal levels in the offspring whose morphine-dependent mothers had received theophylline for 10 days before mating. It is concluded that theophylline may be therapeutically effective in minimizing the adverse consequences of maternal morphine dependence on offspring behavior by restoring normal dopamine receptor expression levels and modulating anxiety. To completely comprehend the underlying mechanisms of this phenomenon, more research is required.

Evaluation of the effect of mesenchymal stem cells injection in the nucleus accumbens on the morphine reinstatement behavior in a conditioned place preference model in Wistar rat: Expression changes of NMDA receptor subunits and NT-3.

Mesenchymal stem cells (MSCs) have been recently shown to improve functional recovery in animal models of CNS disorders and are currently being examined in clinical studies for sclerosis, stroke, and CNS lesions. The activation of endogenous CNS protection and repair mechanisms is unclear. MSC-based approaches are considered a new potential target for neurodegenerative disorders. This study was designed to discover the effect of MSCs injection in the nucleus accumbens (NAc) on the reinstatement of behavior in morphine-induced conditioned place preference (CPP) in male rats. The CPP was induced via intra-peritoneal (i.p.) morphine injection (5 mg/kg) for three consecutive days. After being tested for CPP induction, animals received MSCs or culture medium (DMEM F-12) in their NAc using stereotaxic surgery. Following extinction, a priming dose of morphine (2 mg/kg) was administered to induce reinstatement. Expression of GluN1, GluN2A, and GluN2B subunits of the NMDA receptor and the NT-3 gene in the NAc was assessed on the last day of extinction and following CPP reinstatement. The results showed that local injection of MSCs attenuated reinstatement after receiving a priming dose of morphine, and also shortened the period of CPP extinction. The mRNA expression of the NT-3 gene in the group receiving MSCs was increased compared to control animals, as was observed for GluN1 and GluN2B, but not GluN2A. It is concluded that intra-NAc injection of MSCs may facilitate morphine extinction and alleviate reinstatement behavior which may be via expression changes in NMDA receptor subunits and NT-3 gene.

Exosomes released from U87 glioma cells treated with curcumin and/or temozolomide produce apoptosis in naive U87 cells.

Glioblastoma (GBM) remains the most lethal brain tumor without any curative treatment. Exosomes can mediate cell-to-cell communication, and may function as a new type of targeted therapy. In this study, the therapeutic benefits of exosomes generated by U87 cells treated with curcumin and/or temozolomide were investigated. The cells were cultured and treated with temozolomide (TMZ), curcumin (Cur), or their combination (TMZ+Cur). Exosomes were isolated with a centrifugation kit and characterized using DLS, SEM, TEM, and Western blotting. The levels of exosomal BDNF and TNF-α were measured. Naïve U87 cells were treated with the isolated exosomes, and the effects on apoptosis-related proteins HSP27, HSP70, HSP90, and P53 were assessed. All exosomes, Cur-Exo, TMZ-Exo, and TMZ+Cur-Exo increased cleaved caspase 3, Bax, and P53 proteins, while reducing HSP27, HSP70, HSP90, and Bcl2 proteins. Moreover all treatment groups increased apoptosis in naïve U87 recipient cells. Exosomes released from treated U87 cells had less BDNF and more TNF-α compared to exosomes released from naive U87 cells. In conclusion, we showed for the first time that exosomes released from drug-treated U87 cells could be a new therapeutic approach in glioblastoma, and could reduce the side effects produced by drugs alone. This concept needs to be further examined in animal models before clinical trials could be considered.

Psychometric Characteristics of the Persian Version of the Opiate Dosage Adequacy Scale (ODAS).

Introduction: The opiate dosage adequacy scale (ODAS) is one of the most common assessment tools in studies on substance use disorders, which evaluates the "adequacy" of opiate medication doses in individuals recruited in maintenance approaches. There is no investigation on the Persian version of this questionnaire in Iran. This research validated a Persian version of the ODAS. Methods: The Persian version of the ODAS was translated and revised based on the original scale presented by González-Saiz et al. The psychometric characteristics of the ODAS were assessed via direct interviews. Three trained interviewers questioned 250 patients treated in methadone maintenance clinics in Mazandaran Province (Northern Iran) for more than three months. Internal consistency and factor analysis were conducted using SPSS software, version 24. Results: The internal consistency of ODAS was satisfactory (Cronbach's α=0.81). Across all items, considerable inter-rater reliability was discovered (kappa values between 0.90 and 1). A four-component structure was produced by the factor analysis that accounted for 77.5% of the total variance. Cronbach's α coefficients of the four components of Heroin craving and overmedication, Consumption, objective opiate withdrawal symptoms, and subjective opiate withdrawal symptoms were 0.84, 0.91, 0.83, and 0.74, respectively. Conclusion: The reliability and validity of the Persian version of the ODAS were satisfactory in a sample of methadone maintenance subjects. Highlights: The opiate dosage adequacy scale (ODAS) is a clinical tool for measuring the adequacy of methadone dosesThe Persian version of ODAS has good validity, internal consistency, and inter-rater reliability;The Persian version of the ODAS, as a valid and reliable tool, can be used for the Iranian people under methadone maintenance. Plain Language Summary: In Iran, opioids are among the most common forms of illicit drugs. In opioid maintenance programs, the adequacy of methadone doses has an important effect on treatment outcomes. Clinicians typically assess the adequacy of doses based on the patient's response to the medication. Different tools are used in clinical studies to evaluate it. One of these tools is the ODAS, developed by González-Saiz et al. In the present study, we validated the Persian version of the ODAS for Iranian patients receiving methadone maintenance programs. The results confirmed the four-factor structure of the Persian ODAS and showed its good internal consistency and inter-rater reliability.

A comprehensive view on the quercetin impact on bladder cancer: Focusing on oxidative stress, cellular, and molecular mechanisms.

Bladder cancer (BC) is known as a prevalent genitourinary malignancy and has a significant mortality rate worldwide. Despite recent therapeutic approaches, the recurrence rate is high, highlighting the need for a new strategy to reduce the BC cell progression. Quercetin, a flavonoid compound, demonstrated promising anticancer properties and could be used in the management of various malignancies such as BC. This comprehensive review summarized quercetin's cellular and molecular mechanisms underlying anticancer activities. The study's findings indicated that quercetin prevents the proliferation of the human BC cell line, promotes apoptosis of BIU-87 cells, reduces the expression of p-P70S6K, and induces apoptosis by p-AMPK. Moreover, quercetin restricts tumor growth through the AMPK/mTOR cascade and prevents colony formation of human BC cells by triggering DNA damage. Studying this review article will help researchers better understand quercetin's functional role in the prevention and treatment of BC.

Potential biomarkers of addiction identified by real-time PCR in human peripheral blood lymphocytes: a narrative review.

Addiction-related neurobiological factors could be considered as potential biomarkers. The concentration of peripheral biomarkers in tissues like blood lymphocytes may mirror their brain levels. This review is focused on the mRNA expression of potential addiction biomarkers in human peripheral blood lymphocytes (PBLs). PubMed, EMBASE, Web of Science, Scopus and Google Scholar were searched using the keywords 'addiction', 'biomarker', 'peripheral blood lymphocyte', 'gene expression' and 'real-time PCR'. The results showed the alterations in the regulation of genes such as dopamine receptors, opioid receptors, NMDA receptors, cannabinoid receptors, α-synuclein, DYN, MAO-A, FosB and orexin-A as PBLs biomarkers in addiction stages. Such variations could also be found during abstinence and relapse. PBLs biomarkers may help in drug development and have clinical implications.

There are some peptides and proteins that are considered as non-invasive biomarkers in addiction. The level of such biomarkers in peripheral tissues like blood may be parallel to their concentrations in the brain. Here, we have reviewed the articles that have studied these biomarkers' expression levels in human peripheral blood lymphocytes (PBLs) using the real-time PCR technique. Previous studies have shown that in the process of addiction, some changes might occur in PBLs expression level of factors like dopamine, glutamate and opioid receptors, which are crucial in reward circuits and neurobiology of addiction. Studying the alterations in PBLs concentrations of these parameters (in stages of drug abuse, abstinence and relapse) could help investigators find a promising biomarker, which can help design new treatment strategies.

Effects of Placenta-Derived Human Amniotic Epithelial Cells on the Wound Healing Process and TGF-ß Induced Scar Formation in Murine Ischemic-Reperfusion Injury Model.

BACKGROUND: Pressure ulcers (PUs), a result of ischemic reperfusion (IR) injuries, are prevalent skin problems which show refractoriness against standard therapeutic approaches. Besides, scar formation is a critical complication of ulcers that affects functionality and the skin's cosmetic aspect. The current study aimed to investigate the effects of placenta-derived human amniotic epithelial cells (hAECs), as important agents of regenerative medicine and stem cell therapy, on accelerating the healing of IR ulcers in mice. We also evaluated the effects of these cells on reducing the TGFß-induced scar formation. METHODS: Male Balb/c mice at the age of 6-8 weeks were subjected to three IR cycles. Afterward, the mice were divided into three experimental groups (n = 6 per group), including the control group, vehicle group, and hAECs treatment group. Mice of the treatment group received 100 µL of fresh hAECs 1 × 106 cell/ml suspension in PBS. Afterward, mice were assessed by histological, stereological, molecular, and western blotting techniques at 3, 7, 14, and 21 days after wounding. RESULTS: The histological and stereological results showed the most diminutive scar formation and better healing in the hAECs treated group compared to control group. Furthermore, our results demonstrated that the expression level of Col1A1 on days 3, 14, and 21 in the hAECs treated group was significantly lower than control. Additionally, injection of hAECs significantly reduced the expression level of Col3A1 on days 3, 7, and 21 while increased Col3A1 on the day 14. Otherwise, in the hAECs treated group, the expression levels of VEGFA on days 7 and 14 were higher, which showed that hAECs could promote angiogenesis and wound healing. Also, cell therapy significantly lowered the protein levels of TGF-ß1 on day 14, while the protein level of TGF-ß3 on day 14 was significantly higher. This data could demonstrate the role of hAECs in scar reduction in IR wounds. CONCLUSION: These results suggest that hAECs can promote re-epithelialization and wound closure in an animal model of PU. They also reduced scar formation during wound healing by reducing the expression of TGF-ß1/ TGF-ß3 ratio.

Microfluidics for detection of exosomes and microRNAs in cancer: State of the art.

Exosomes are small extracellular vesicles with sizes ranging from 30-150 nanometers that contain proteins, lipids, mRNAs, microRNAs, and double-stranded DNA derived from the cells of origin. Exosomes can be taken up by target cells, acting as a means of cell-to-cell communication. The discovery of these vesicles in body fluids and their participation in cell communication has led to major breakthroughs in diagnosis, prognosis, and treatment of several conditions (e.g., cancer). However, conventional isolation and evaluation of exosomes and their microRNA content suffers from high cost, lengthy processes, difficult standardization, low purity, and poor yield. The emergence of microfluidics devices with increased efficiency in sieving, trapping, and immunological separation of small volumes could provide improved detection and monitoring of exosomes involved in cancer. Microfluidics techniques hold promise for advances in development of diagnostic and prognostic devices. This review covers ongoing research on microfluidics devices for detection of microRNAs and exosomes as biomarkers and their translation to point-of-care and clinical applications.

Association of SHANK3 Gene Polymorphism and Parkinson Disease in the North of Iran.

INTRODUCTION: Parkinson Disease (PD), the second most common chronic neurodegenerative disorder, is characterized by tremor, bradykinesia, rigidity, and postural instability. SHANK3 (SH3 and multiple ankyrin repeat domain 3) belongs to the extremely conserved ProSAP/Shank family of synaptic scaffolding proteins. Meanwhile, rs9616915 is a non-synonymous SNP (T>C) located in the exon 6 of the SHANK3 gene, which induces substitution of isoleucine to threonine and affects the function of the resulted protein. The present study aimed to evaluate whether rs9616915 polymorphism of SHANK3 is involved in the susceptibility to PD. METHODS: The study subjects were 100 patients diagnosed with PD and 100 control volunteers. The obtained samples were evaluated by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: A significant association was found in genotype distribution between cases and controls. Individuals with TC genotype had increased risk of PD (P=0.035, OR=1.98, 95% CI=1.04 - 3.74). No significant difference was found in allele distribution (P=0.7). CONCLUSION: The findings suggest that the SHANK3 rs9616915 polymorphism is associated with an increased risk of PD in the population. Further studies are needed to confirm the role of the SHANK3 gene in PD.