The role of inflammasome complex in ischemia-reperfusion injury.

Ischemia-reperfusion injury refers to a temporary interruption of blood flow in a tissue. Restoration of blood flow initiates the inflammation in tissue causing ischemic damage through the activation of a multiprotein complex termed inflammasome. The complex contains a receptor, mainly a member of nucleotide oligomerization domain-like receptors, that receives danger signals. The receptor is oligomerized as a response to danger signals and then the apoptosis-associated speck-like protein containing a caspase recruitment domain and procaspase protein are added to the oligomerized receptors to form the inflammasome complex. In the next step, the isolated procaspase is converted into an active caspase molecule that initiates the inflammation through the release of interleukin-1ß and interleukin-18. The inflammasome has an important role in the pathogenesis of ischemia-reperfusion injury in different tissues. Here, we summarized the role of inflammasome in the pathogenesis of ischemia-reperfusion of brain, liver, kidney, and heart. Moreover, we highlighted the expression of inflammasome components, the mechanisms involved in activation of the complex, and its inhibition as an optimistic therapeutic technique in ischemia-reperfusion injuries.

Influenza vaccine: Where are we and where do we go?

The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross-reactive immune response. The lack of viral genome in VLP and M2e-based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome-based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.

Exosomes and microRNAs: New potential therapeutic candidates in Alzheimer disease therapy.

Exosomes are biological nanocarriers which could be involved in a variety of basic physiological events. They exert their effects via targeting their cargos (i.e., DNAs, messenger RNAs, microRNAs [miRNAs], and proteins) to host cells, which led to change behaviors of recipient cells. One of the important aspects of exosomes is the roles of them in disease conditions. Increasing evidence indicated that exosomes are one of the main players in Alzheimer's disease (AD) pathogenesis. Hence, it seems that these nanocarriers could be used as diagnostic and therapeutic biomarkers in AD treatment. Another important player in AD pathogenesis is miRNA. MiRNAs are short noncoding RNAs which exert their effects as epigenetic regulators. These molecules involved in different stages of AD. Therefore, miRNAs could be used as prognostic, diagnostic, and therapeutic biomarkers in AD. Here, we summarized various roles of exosomes and application of them in AD pathogenesis. Moreover, we highlighted the utilization of miRNAs as a therapeutic option in AD therapy.

Effect of curcumin on glioblastoma cells.

Curcumin is a polyphenolic compound derived from Curcumin longa L. There are growing bodies of evidence revealing the antitumor effect of curcumin in different tumors; although the molecular mechanism behind this inhibition in glioblastoma multiform (GBM) still remains unclear. Here we investigated the antitumor activity of nano micelles curcumin compared with erlotinib in U-373 cells in monolayer cell cultures and spheroids models. Furthermore, we characterized affecting cell cycle perturbation, as well as apoptosis induction in GBM cells. The antiproliferative activity of nano micelles curcumin and erlotinib were assessed in monolayer and spheroid models. The influence of the cell cycle and expression levels of nuclear factor κB (NF-κB) and Wnt/ß-catenin pathway was checked. Nano micelles curcumin suppressed cell growth in U-373 cells via modulation of Wnt and NF-κB pathways. Moreover, cells developed an early G2/M cell cycle arrest followed by sub-G1 apoptosis and apoptotic bodies formation posttreatment with nano micelles curcumin and erlotinib. In the core signaling pathways of GBM, nano micelles curcumin either significantly influences the NF-κB pathway by decreasing p-65 expression or significantly inhibits the Wnt/ß-catenin pathway by declining cyclin D1 expression. In conclusion, we have shown that nano micelles curcumin effectively prevent proliferation, and invasion of GBM cells through perturbation of Wnt/ß-catenin and NF-κB pathways, suggesting further investigations on the therapeutic application of this novel anticancer drug in in vivo models.

Ruptured inferior vena cava aneurysm in the setting of mural vascular malformation: A case report.

Aneurysm of the inferior vena cava is a rare anomaly with a very few reported cases worldwide. We report the case of a 26-years-old man with acute severe abdominal pain and hypovolemic shock following an episode of syncope. Ultrasonography showed a fusiform aneurysmal dilation of the infra-hepatic inferior vena cava (IVC), with a large saccular portion at its posterolateral wall and mural thrombosis. Abdominal computed tomography scan revealed extension to the right renal vein and adhesion to the right kidney. The saccular aneurysm and the right kidney were resected, and anatomopathological examination revealed a cavernous hemangioma. All symptoms disappeared after surgery. This is the first reported case of symptomatic congenital saccular aneurysm of the IVC due to mural vascular malformation and with involvement of the right kidney leading to nephrectomy.

Breast cancer diagnosis: Imaging techniques and biochemical markers.

Breast cancer is a complex disease which is found as the second cause of cancer-associated death among women. Accumulating of evidence indicated that various factors (i.e., gentical and envirmental factors) could be associated with initiation and progression of breast cancer. Diagnosis of breast cancer patients in early stages is one of important aspects of breast cancer treatment. Among of various diagnosis platforms, imaging techniques are main diagnosis approaches which could provide valuable data on patients with breast cancer. It has been showed that various imaging techniques such as mammography, magnetic resonance imaging (MRI), positron-emission tomography (PET), Computed tomography (CT), and single-photon emission computed tomography (SPECT) could be used for diagnosis and monitoring patients with breast cancer in various stages. Beside, imaging techniques, utilization of biochemical biomarkers such as proteins, DNAs, mRNAs, and microRNAs could be employed as new diagnosis and therapeutic tools for patients with breast cancer. Here, we summarized various imaging techniques and biochemical biomarkers could be utilized as diagnosis of patients with breast cancer. Moreover, we highlighted microRNAs and exosomes as new diagnosis and therapeutic biomarkers for monitoring patients with breast cancer.

MicroRNAs in retinoblastoma: Potential diagnostic and therapeutic biomarkers.

Retinoblastoma (Rb) is known as one of important childhood malignancies which due to inactivation of the RB gene (tumor suppressor gene in various patients). The early detection of Rb could provide better treatment for Rb patients. Imaging techniques (e.g., MRI and CT) are known as one of effective diagnosis approaches for detection of patients with Rb. It has been shown that utilization of imaging techniques is associated with some limitations. Hence, identification of new diagnosis approaches might provide a better treatment for Rb patients. Identification of new biomarkers could contribute to better understanding of pathogenesis events involved in Rb and provide new insights into design better treatment approaches for these patients. Among the various biomarkers, microRNAs (miRNAs) have emerged as attractive tools for Rb detection. miRNAs are one classes of small non-coding RNAs which could anticipate in a variety of biological process via targeting sequence of cellular and molecular pathways. Deregulations of these molecules are associated with cancerous condition. Multiple lines of evidence indicated that deregulation of various miRNAs involved in various stages of Rb. Here, we summarized a variety of tissue-specific and circulating miRNAs involved in Rb pathogenesis which could be used as diagnostic, prognostic, and therapeutic biomarkers in Rb patients.

MicroRNA: Relevance to stroke diagnosis, prognosis, and therapy.

Stroke is a life-threatening disease that accounts for a considerable burden of mortality in both developing and developed world. Identification of specific biomarkers for stroke and its outcomes can greatly contribute to improved care of patients. MicroRNAs (miRNAs) are known as novel biomarkers that could be used as diagnostic, prognostic, and therapeutic biomarkers. Various studies have shown that miRNAs have key roles in the pathogenesis of stroke, and its complications and outcomes. In addition, there is evidence showing that mesenchaymal stromal cell-derived exosomes containing miRNAs can be used for monitoring and treatment of various diseases such as stroke. Here, we summarized various aspects of miRNA applications in different stages of stroke.

State of the art in microRNA as diagnostic and therapeutic biomarkers in chronic lymphocytic leukemia.

Early diagnostic is one of the most important steps in cancer therapy which helps to design and choose a better therapeutic approach. The finding of biomarkers in various levels including genomics, transcriptomics, and proteomics levels could provide better treatment for various cancers such as chronic lymphocytic leukemia (CLL). The CLL is the one of main lymphoid malignancies which is specified by aggregation of mature B lymphocytes. Among different biomarkers (e.g., CD38, chromosomes abnormalities, ZAP-70, TP53, and microRNA [miRNA]), miRNAs have appeared as new diagnostic and therapeutic biomarkers in patients with the CLL disease. Multiple lines of evidence indicated that deregulation of miRNAs could be associated with pathological events which are present in the CLL. These molecules have an effect on a variety of targets such as Bcl2, c-fos, c-Myc, TP53, TCL1, and STAT3 which play critical roles in the CLL pathogenesis. It has been shown that expression of miRNAs could lead to the activation of B cells and B cell antigen receptor (BCR). Moreover, exosomes containing miRNAs are one of the other molecules which could contribute to BCR stimulation and progression of CLL cells. Hence, miRNAs and exosomes released from CLL cells could be used as potential diagnostic and therapeutic biomarkers for CLL. This critical review focuses on a very important aspect of CLL based on biomarker discovery covers the pros and cons of using miRNAs as important diagnostics and therapeutics biomarkers for this deadly disease.

A comparison of pain control and complications using three different ways of anesthesia in patients undergoing transrectal ultrasound-guided prostate biopsy.

BACKGROUND: We aim to compare the degree of pain control and complications in three types of anesthesia using periprostatic nerve block (PPNB) plus intrarectal local anesthesia (IRLA), low-dose spinal anesthesia, and intravenous (IV) sedation in patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy. MATERIALS AND METHODS: In this clinical trial study, 106 patients were participated from December 2015 to December 2016 at Alzahra Hospital, Isfahan, Iran. Patients were randomly allocated into three groups to receive PPNB plus IRLA (n = 36), low-dose spinal anesthesia (n = 35) and IV sedation (n = 35) before TRUS-guided prostate biopsy. Pain scores were recorded using a 10 point visual analog scale right after the biopsy was done. Early and late complications were assessed using a questionnaire after the procedure and in follow-up of patients. RESULTS: Overall, the pain score in the low-dose spinal anesthesia group was significantly lower than PPNB plus IRLA and IV sedation groups (P < 0.001). The differences in pain scores between PPNB plus IRLA group and IV sedation group were not significant (P = 0.30). Urinary retraction and fever were significantly more frequent in low-dose spinal anesthesia and IV sedation, retrospectively (P = 0.04, P = 0.03). No significant difference in late complications was found among the groups. CONCLUSION: This study demonstrates that low-dose spinal anesthesia is superior to PPNB plus IRLA and IV sedation in terms of pain controlling and was associated with higher tolerance of the examination and patient comfort.

Effectiveness of extracorporeal shockwave therapy for chronic Achilles tendinopathy: A randomized clinical trial.

BACKGROUND: In this study, we aimed to evaluate the effectiveness of extracorporeal shockwave treatment (ESWT) on pain and ankle-hindfoot scale of the American Orthopedic Foot and Ankle Society (AOFAS) score of patients with chronic Achilles tendinopathy (AT). MATERIALS AND METHODS: In this double-blind clinical trial, 43 patients with chronic AT were selected and randomly allocated in two groups to receive a basic treatment with ESWT or sham SWT (radial and focused shock waves, four sessions once a week for 4 weeks). AOFAS and pain scores for each patient were recorded at baseline (before intervention), immediately after intervention, and 4 and 16 weeks after intervention using AOFAS and visual analog scale (VAS) scaling method. RESULTS: A total of 43 patients (22 ESWT and 21 sham SWT) were participated in this study. Both groups improved during the treatment and follow-up period. The mean VAS score decreased from 7.55 to 3 in the intervention group and from 7.70 to 4.30 in the sham SWT group. Mean AOFAS and VAS scores were significantly different between ESWT and no ESWT groups at 16 weeks of follow-up (P = 0.013) (P = 0.47). There was no significant difference in terms of AOFAS and VAS scores between both the groups in the other follow-up times. CONCLUSION: Overall, ESWT causes decrease in VAS score and increase in AOFAS score. However, due to the small sample size, the results were not statistically significant. It is recommended to plan more interventional studies with larger sample size in the future.

Molecular Imaging and Oral Cancer Diagnosis and Therapy.

Oral cancer is known as one of relatively common type of cancer worldwide. Despite the easy access of the oral cavity to examination, oral tumors are diagnosed in more advanced stages of the disease. Imaging techniques have been recently emerged as non-invasive approaches to detect molecular and cellular changes in living cells and organisms. These techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) could help physicians to screen patients with oral tumors particularly oral squamous cell carcinoma (OSCC) in early stage of the disease. In this review, we discuss that early detection and diagnosis of oral tumors through using more robust and precise imaging techniques and a variety of cellular/molecular biomarkers not only could lead to more effective and less aggressive form of treatment for the disease but also could improve survival rates and lower treatment costs. J. Cell. Biochem. 118: 3055-3060, 2017. © 2017 Wiley Periodicals, Inc.

Effect of Vitamin D deficiency treatment on thyroid function and autoimmunity markers in Hashimoto's thyroiditis: A double-blind randomized placebo-controlled clinical trial.

BACKGROUND: The link between autoimmune thyroid diseases and Vitamin D deficiency has been reported. However, there are controversies in this regard. We conducted a double-blind randomized placebo-controlled clinical trial to investigate the effect of Vitamin D deficiency treatment on thyroid function and autoimmunity marker (thyroid peroxidase antibody [TPO-Ab]) in patients with Hashimoto's thyroiditis. MATERIALS AND METHODS: Fifty-six patients with Hashimoto's thyroiditis and Vitamin D deficiency (25-hydroxyvitamin D level ≤20 ng/mL) were randomly allocated into two groups to receive Vitamin D (50000 IU/week, orally) or placebo for 12 weeks, as Vitamin D-treated (n = 30) and control (n = 26) groups, respectively. TPO-Ab, thyroid-stimulating hormone (TSH), parathormone, calcium, albumin, and creatinine concentrations were compared before and after trial between and within groups. The data were presented as mean (standard error [SE]) and analyzed by appropriate tests. RESULTS: Mean (SE) of Vitamin D was increased in Vitamin D-treated group (45.5 [1.8] ng/mL vs. 12.7 [0.7] ng/mL, P = 0.01). Mean (SE) of TPO-Ab did not significantly change in both groups (734 [102.93] IU/mL vs. 820.25 [98.92] IU/mL, P = 0.14 in Vitamin D-treated and 750.03 [108.7] [IU/mL] vs. 838.07 [99.4] [IU/mL] in placebo-treated group, P = 0.15). Mean (SE) of TSH was not changed in both groups after trial, P = 0.4 and P = 0.15 for Vitamin D-treated and control groups, respectively. No significant difference was observed between two study groups in none studied variables (P > 0.05). CONCLUSION: Vitamin D treatment in Vitamin D deficient patients with Hashimoto's thyroiditis could not have significant effect on thyroid function and autoimmunity.

Systematic review and metaanalysis of air pollution exposure and risk of diabetes.

The present systematic review and metaanalysis of published observational studies was conducted to assess the health effects of exposure to air pollution on diabetes risk. Online databases were searched through January 2013, and the reference lists of pertinent articles reporting observational studies in humans were examined. Pooled relative risks and 95 % confidence intervals were calculated with a random-effects model. Exposure to air pollution was associated with slight increase in risk of diabetes and susceptibility of people with diabetes to air pollution. These results were consistent between time-series, case-crossover and cohort studies and between studies conducted in North America and Europe. The association between exposure to air pollution and diabetes was stronger for gaseous pollutants than for particulate matter. Our metaanalysis suggests that exposure to air pollution may be a risk factor for diabetes and increase susceptibility of people with diabetes to air pollution.

Ti3C2 MXene-based nanozyme as coreaction accelerator for enhancing electrochemiluminescence of glucose biosensing.

Delamination of the exfoliated multilayer MXenes with electro-catalysts, not only leads to increasing surface area for high electrochemiluminescent (ECL) signal tracer loading but also provides highly sensitive achievements in a coreaction accelerator manner. To this end, herein, we used bromophenol blue (BPB)-delaminated multilayer Ti3C2 MXene as both a coreaction accelerator to promote the electrochemiluminescent (ECL) reaction rate of luminol (LUM) and the co-reactant H2O2 and a substrate for retaining high loading of glucose oxidase (GOx)-conjugated polyethylene imine (PEI) along with luminophore species into more open structure of Ti3C2 MXene for sensitive detection of glucose. In the presence of glucose, in situ generating H2O2 product through a GOx-catalyzed process could produce abundant •OH radicals via the peroxidase-like activity of the BPB@Ti3C2 in the LUM ECL reaction. Moreover, decreasing the distance between the high-content LUM into the BPB@Ti3C2 and the generated •OH, minimizes the decomposition of highly active •OH, providing a superb ECL signal. Last, the proximity of incorporated GOx into the delaminated Ti3C2 MXene near the electrode allows efficient electron transfer between the electrode and enzyme. The integration of such amplifying effects endowed high sensitivity and excellent selectivity for glucose with a low limit of detection of 0.02 µM in the wide range of 0.01 µM-40,000 µM, enabling the feasibility of the glucose analysis in human serum samples. Overall, the enhanced ECL based on the BPB@Ti3C2 opens a new horizon to develop highly sensitive MXene-based ECL toward the field of biosensors.

Efficacy of metformin on the body mass index of patients under treatment with SSRI drugs referred to psychiatry clinics of Rasht.

Objective: Serotonin reuptake inhibitors cause weight gain, leading to drug discontinuation, relapse, and worsening of symptoms. This study aims to investigates the effect of metformin on weight loss, anthropometric indicators and laboratory assessments in patients of Rasht city. Methods: This clinical trial study with parallel-group design was organized based on 60 patients in treatment group (undergoing metformin) and 60 patients in control group (undergoing routine treatment) in Shafa hospital during July 2019 to January 2020. First, we determined the overweight patients. After that, a psychiatric assistant randomly divides them into two groups, intervention and control. Both groups of patients will be explained in terms of how they were studied and whether or not they received metformin. In order to statistical analysis of collected data, we applied the Mann-Whitney U test and repeated measures ANOVA. For conducting all analysis, the IBM SPSS Statistics 28 software was used. Results: The mean BMI and abdominal circumference decreased significantly in the intervention group. The wrist circumference in the intervention group decreased over time, but this difference was not statistically significant. There was no statistically significant difference between the average changes of the mean values of the laboratory assessment among the group. Conclusion: Weight gain can cause problems related to compliance with treatment and anxiety and depression. On the other hand, in our study, metformin was not superior to lifestyle improvements and practicing preventive methods for weight control. Further research on SSRIs and monitoring of anthropometric indices is recommended.

Gastric Cancer Diagnosis: From Imaging Techniques to Biochemical Biomarkers.

Gastric cancer (GC) has been found to be the second leading cause of cancer-associated deaths in the world, and is usually detected in the advanced stages. It has been shown that surgery is the major therapeutic approach in the treatment of subjects with GC. Hence, early and fast diagnosis of this malignancy is very important for good subject outcomes. Non-invasive diagnostic platforms, including evolutionary endoscopy and positron emission tomography (PET), are employed for the diagnosis of subjects with GC. Along with imaging techniques, the utilization of biomarkers has emerged as a new diagnosis option for early and fast detection of GC. Multiple lines of evidence have revealed a variety of biomarkers, including microRNAs, exosomes, circulating tumor cells, circular RNAs, cell free DNAs, and various proteins, which could be used as diagnostic biomarkers in patients with GC. Taken together, these findings suggest that the joint application of imaging techniques and different biomarkers could be introduced as a new detection approach in the treatment and screening response to therapy in the subjects with GC. Herein, we have summarized various imaging techniques and biomarkers as powerful tools in the detection of GC.

Cervical Cancer Diagnosis: Insights into Biochemical Biomarkers and Imaging Techniques.

Cervical malignancy is known as one of the important cancers which is originated from cervix. This malignancy has been observed in women infected with papillomavirus who had regular oral contraceptives, multiple pregnancies, and sexual relations. Early and fast cervical cancer diagnosis is known as two important aspects of cervical cancer therapy. Several investigations indicated that early and fast detection of cervical cancer could be associated with better treatment process and increasing survival rate of patients with this malignancy. Imaging techniques are very important diagnosis tools that could be employed for diagnosis and following responses to therapy in various cervical cancer stages. Multiple lines of evidence indicated that utilization of imaging techniques is related to some limitations (i.e. high cost, and invasive effects). Hence, it seems that along with using imaging techniques, finding and developing new biomarkers could be useful in the diagnosis and treatment of subjects with cervical cancer. Taken together, many studies showed that a variety of biomarkers including, several proteins, mRNAs, microRNAs, exosomes and polymorphisms might be introduced as prognostic, diagnostic and therapeutic biomarkers in cervical cancer therapy. In this review article, we highlighted imaging techniques as well as novel biomarkers for the diagnosis of cervical cancer.

Dorsal midbrain involvement in MRI as a core clinical manifestation for NMOSD diagnosis.

BACKGROUND: Few data are available on the prevalence of midbrain lesions among NMOSD patients. The study aimed to address the frequency of midbrain lesions, especially dorsal midbrain involvement, among a group of NMOSD patients. METHODS: The medical records of 108 NMOSD patients were reviewed, who were registered at the Al-Zahra MS Clinic, Isfahan, Iran. The patients´ information including sex, age, first recorded chief complaint, and midbrain lesion presence in the first brain MRI was collected. RESULTS: Out of the 108 NMOSD patients, eight had midbrain lesions in their first brain MRI (7.4%). Of these patients, 50% were male and 50% were female, with the mean age being 35.25 ± 12.17 years. The most frequent first chief complaints included diplopia due to incomplete third nerve palsy and vertigo. The brain MRIs of the patients showed symmetric dorsal midbrain involvement in all the patients, and enhancement was discovered in only one of the brain MRIs. CONCLUSION: Among the patients, 7.4% presented midbrain involvement at onset. Therefore, midbrain lesions should also be considered as a possible core clinical manifestation in the NMOSD diagnostic criteria.

Joint Application of Magnetic Resonance Imaging and Biochemical Biomarkers in Diagnosis of Multiple Sclerosis.

Multiple Sclerosis (MS), an autoimmune disorder associated with spinal cord and brain, chiefly affects the white matter. Regarding the complexity as well as heterogenic etiology of this disease, the treatment of MS has been a challenging issue up to now. Researchers are working to develop new therapeutic strategies and drugs as complementary therapies. MS diagnosis significantly depends on the findings of Magnetic Resonance Imaging (MRI) examination. In this imaging technique, gadolinium is used as a contrast agent to reveal active plaques intending to destroy the bloodbrain barrier. It also detects plaques that are not correlated with the neurological symptoms. It has been attempted to determine biomarkers related to different dimensions of MS in various organizational hierarchy levels of the human anatomy (i.e., cells, proteins, RNA, and DNA). These biomarkers are appropriate diagnostic tools for MS diagnosis. In this review, we summarized the application of MRI and biochemical biomarkers to monitor MS patients. Moreover, we highlighted the joint application of MRI and biomarkers for the diagnosis of MS subjects.