Altered Expression of B Cell Receptor Signaling Pathway Genes in Peripheral Blood of Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease and has adverse implications. The exact mechanism of its pathogenesis is not fully understood and remains to be elucidated. In the current study we aimed to identify key genes that can serve as potential biomarkers and therapeutic targets for MS and shed light on pathogenesis mechanisms involved in MS. We analyzed a gene expression dataset (GES21942) and found 266 differentially expressed genes (DEGs) including 183 upregulated and 83 downregulated genes in MS patients compared to controls. Then we conducted pathway enrichment on DEGs and selected the top enriched pathway i.e., B cell receptor signaling pathway, and 5 genes of this pathway (CR2, BLK, BLNK, RASGRP3, and KRAS) for further investigation in our clinical samples. We recruited 50 MS patients and 50 controls and assessed the expression of selected genes in the circulation of patients versus controls. Expression of CR2, BLK, BLNK, and RASGRP3 were significantly higher in MS cases compared with controls. There was no significant difference in expression of KRAS between patients and controls. All of the selected genes with differential expression had noticeable diagnostic power and CR2 was the most robust gene in differentiating MS cases from controls. Additionally, a combination of genes resulted in enhanced diagnostic power. Collectively our results suggest that the B cell receptor signaling pathway and the selected genes from this pathway may be implicated in the pathogenesis of MS and each of these genes can be considered as potential diagnostic biomarkers and therapeutic targets.

Enhancing anti-amyloidogenic properties and antioxidant effects of Scutellaria baicalensis polyphenols through novel nanoparticle formation.

Protein aggregation and oxidative stress have gained significant research attention due to their association with a group of diseases known as amyloidosis. Among the strategies developed to prevent amyloidosis, utilization of polyphenols stands out as one of the most commonly employed approaches. Scutellaria baicalensis is renowned as one of the foremost herbal sources of polyphenols. In this study, we employed a direct oxidative pyrolysis method for polymerizing S. baicalensis's polyphenols (SBPPs) after their extraction, resulting in the formation of novel SBPPs nanoparticles. Upon polymerization, SBPPs nanoparticles showed remarkable properties including heightened water solubility, increased surface area, modified surface functional groups, and enhanced stability. As a result of these diverse factors, there was a considerable enhancement in the anti-amyloidogenic properties and antioxidant effects of SBPPs nanoparticles compared to its bulk form. The fibrillation kinetics, AFM images, and cytotoxicity assays strongly indicate that SBPPs nanoparticles are more effective than SBPPs at preventing amyloid fibril formation and associated cell toxicity. Additionally, SBPPs nanoparticles demonstrated more effective prevention of reactive oxygen species (ROS) production. In conclusion, the use of SBPPs in nanoparticle form presents a promising strategy to enhance anti-amyloidogenic properties, mitigate oxidative stress, and offer potential therapeutic benefits for amyloidosis-related diseases.

Prediction and Validation of Hub Genes Related to Major Depressive Disorder Based on Co-expression Network Analysis.

Major depressive disorder (MDD) is generally among the most prevalent psychiatric illnesses. Significant advances have occurred in comprehension of the MDD biology. However, it is still essential to recognize new biomarkers for potential targeted treatment of patients with MDD. The present work deals with in-depth comparative computational analyses to obtain new insights, such as gene ontology and pathway enrichment analyses and weighted gene co-expression network analysis (WGCNA) through gene expression dataset. The expression of selected hub-genes was validated in MDD patients using quantitative real-time PCR (RT-qPCR). We found that MDD progression includes the turquoise module genes (p-value = 1e-18, r = 0.97). According to gene enrichment analysis, the cytokine-mediated signaling pathway mostly involves genes in this module. By selection of four candidate hub-genes (IL6, NRG1, TNF, and BDNF), RT-qPCR validation was performed. A significant NRG1 downregulation was revealed by the RT-qPCR outcomes in MDD. In MDD patients, TNF and IL6 expression were considerably higher, and no considerable differences were found in the BDNF expression. Ultimately, based on ROC analyses, IL6, NRG1, and TNF had a higher MDD diagnostic performance. Therefore, our study presents information on the intricate association between MDD development and cytokine-mediated signaling, thus providing new rationales to develop new therapeutic approaches.

One-pot rapid visual detection of E. coli O157:H7 by label-free AuNP-based plasmonic-aptasensor in water sample.

Access to clean water for irrigation and drinking has long been a global concern. The need for fast, precise, and cost-effective methods to detect harmful bacteria like Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is high due to the potential for severe infectious diseases. Fortunately, recent research has led to developing and utilizing rapid bacterial detection methods. The creation of an aptamer-based biosensor (aptasensor) for the detection of E. coli O157:H7 using label-free aptamers and gold nanoparticles (AuNPs) is described in this study. The specific aptamers that can detect target bacteria are adsorbed on the surface of unmodified AuNPs to form the aptasensor. The detection is performed by target bacterium-induced aptasensor aggregation, which is associated with a red-to-purple color change under high-salt circumstances. We devised a quick and easy method for detecting bacteria using an anti-E. coli O157:H7 aptamer without the need for specialized equipment or pretreatment processes like cell lysis. The aptasensor could identify target bacteria with only as few as 250 colony-forming units (CFU)/ml in 15 min or less, and its specificity based on our test was 100%. This method not only provides a fast direct preparation process but also exhibits remarkable proficiency in promptly identifying the intended target with a heightened level of sensitivity and specificity. Therefore, it can serve as an intelligent tool for monitoring water reservoirs and preventing the transmission of infectious diseases associated with EHEC.

Amlodipine alleviates renal ischemia/reperfusion injury in rats through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.

BACKGROUND: Previously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure the effect of amlodipine on renal ischemia/reperfusion (I/R) injury and find the underlying mechanisms. MATERIALS AND METHODS: Bilateral renal I/R was induced by clamping the hilum of both kidneys for 30 min. The first dose of amlodipine 10 mg/kg was gavaged before anesthesia. The second dose of amlodipine was administered 24 h after the first dose. Forty-eight hours after I/R, rats were anesthetized, and their blood and tissue specimens were collected. RESULTS: Amlodipine significantly decreased the elevated serum levels of creatinine and blood urea nitrogen (BUN) and mitigated tissue damage in hematoxylin & eosin (H&E) staining. Amlodipine strongly reduced the tissue levels of malondialdehyde (MDA), interleukin 1ß (IL1ß), and tumor necrosis factor α (TNF-α). Amlodipine enhanced antioxidant defense by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2. Furthermore, amlodipine significantly improved mitochondrial biogenesis by promoting Sestrin2/peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway. It also enhanced autophagy and attenuated apoptosis, evidenced by increased LC3-II/LC3-I and bcl2/bax ratios after renal I/R. CONCLUSION: These findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.

PiRNA Biogenesis and Their Role in Human Cancers and Other Diseases: A Narrative Review.

PIWI-interacting RNAs (piRNAs) with the length of approximately 26-30 nucleotides are a distinct class of small non-coding RNAs that mainly expressed in the animal gonads. Other small RNAs originate from double stranded precursors but piRNAs derive from long single-stranded primary transcripts, which expressed from distinct genomic regions. piRNAs are involved in silencing of mobile elements named transposons and their main role is germline maintenance. Recent studies have opened new insights on biological and clinical significance of piRNAs in various diseases. Abnormal expression of piRNAs is a remarkable feature in many diseases especially human cancers, which emphasize on their important biological role in disease progression. Furthermore, they can be served as biomarkers and therapeutic targets for tumor diagnostics and treatment. In this review, we explained piRNAs characteristics, biogenesis process and functions, discuss new findings about involvement of these elements in various disease and their potential to be used as diagnostic biomarkers.

Correction to: Development of dual-emission cluster of Ag atoms for genetically modified organisms detection.

The published version of this article, unfortunately, contains error in the affiliation. The authors express their sincere apology and corrected the affiliations in this article.

Development of dual-emission cluster of Ag atoms for genetically modified organisms detection.

A DNA-silver nanocluster with two distinct emissions is devised, in which this unique modality has been exploited to develop a novel nanosensor for transgenic DNA detection. TEM and fluorescence analysis revealed the formation of Ag nanoclusters with a size of around 2 nm, which exhibit dual-emissions at 550 nm (green) and 630 nm (red). Moreover, in the presence of the target sequence (CaMV 35S promoter) from the transgenic plant, the nanoclusters showed an enhancement in the green emission and a reduction in the red emission. This property provided a ratiometric-sensing platform which lacks unavoidable noises. The ratio of green to red fluorescence emission (G/R) of the nanoclusters exhibited a linear relation with the target concentration in the range 10 to 1000 nM. However, the control DNA did not affect this ratio, which clearly confirmed the selective response of the designed nanosensor. This sensing platform had a detection limit of 1.5 nM and identified the DNA of transgenic soybeans within a short time. The mechanistic evaluation of the nanoclusters further revealed the role of protonated cytosine bases in the dual emission behavior. Finally, unique features of the designed nanosensor may improve the current approaches for the development and manufacturing of GMO detection tools.

Enhancing Catecholase Activity of a Recombinant Human Tyrosinase Through Multiple Strategies.

BACKGROUND: Tyrosinases are copper-containing enzymes that initiate the melanin synthesis. They catalyze the direct oxidation of L-tyrosine or L-DOPA into L-DOPAquinone. OBJECTIVES: In present study, we aimed to obtain a recombinant tyrosinase with enhanced catecholase activity through site-directed mutagenesis. MATERIALS AND METHODS: The coding sequence of human tyrosinase along with native signal sequence was cloned into pET-28a (+). BL-21 was used as expression host and recombinant protein was purified by Ni-NTA resins. Site-directed mutagenesis was performed on M374 residue to achieve four mutants: M374D, M374T, M374K and M374R. Chloride ions (Cl-) were removed from all solutions, and an extra amount of Cu2+ ions was added to recombinant tyrosinases by a novel technique during the purification process. Removal of Cl- ions and addition of extra Cu2+ ions tripled catecholase activity of the recombinant protein. Therefore, all mutants were obtained under similar conditions. RESULTS: Although all the mutants presented higher catecholase activity in comparison to the wild-type enzyme, a significant increase in catecholase activity of the M374D mutant was observed ‒ 13.2-fold. In silico modeling suggested that a de novo hydrogen bond occurs between side chain carboxyl oxygens of D374 and H367 in M374D. In the wild-type tyrosinase, the peptide oxygen atom of M374 is responsible for hydrogen bonding with H367. CONCLUSIONS: Our data suggests that M374D mutational variant has applications in different areas such as agriculture, industry, and medicine.

Design and Application of A Bioluminescent Biosensor for Detection Of Toxicity Using Huh7-CMV-Luc Cell Line.

Cell-based biosensors (CBBs) are becoming important tools for biosecurity a lications and rapid diagnostics in food microbiology for their unique capability of detecting hazardous materials. Pollutants, such as heavy metals and chemicals, are now considered as a global threat and are associated with detrimental health outcomes. Fast and accurate detection of pollutants is essential to reduce these threats. In this study, the enhancer sequence of human cytomegalovirus (hCMV) IE genes cloned upstream of luc gene in PGL4.26 plasmid, in order to increase basal luciferase activity. This recombinant vector was transfected into Huh7 cell line and after 21 days of treatment with Hygromycin B selectable marker, stable cell line was generated. After several passages, cells containing this vector showed high luciferase activity in normal conditions without any induction following to overexpression of luc gene. Huh7-CMV-luc cell line was able to detect the slightest changes in ATP level, due to the effect of different toxins on the cell which disrupt cellular respiration and ATP production processes. In order to investigate the sensitivity of the cell line, the cells were incubated with 0.1-10 µM of chemical toxins affecting ATP production. These toxins affect luciferase activity in a dose dependent manner, with maximal sensitivity approximately about 0.2 µM to toxin concentrations. Additionally, this biosensor provided a rapid detection as early as 4 h in response to the toxicants. Whole cell biosensors like huh7-CMV-luc cell line can be considered as a powerful tool for the sensitive and efficient monitoring of general toxins, drugs, and environmental pollutants.

The comparison of the effectiveness between different doses of local methylprednisolone injection versus triamcinolone in Carpal Tunnel Syndrome: a double-blind clinical trial.

PURPOSE: Local corticosteroid injection is one of the most prevalent methods in treating carpal tunnel syndrome (CTS). However, the most efficient substance and its appropriate dosage remain controversial. In the present double-blind randomized controlled trial, the efficacy and safety of local injection of two corticosteroids (triamcinolone and methylprednisolone) were compared at two different dosages, 20 and 40 mg. PATIENTS AND METHODS: We consecutively included 80 patients with mild or moderate CTS and randomly assigned them to four groups: 20 or 40 mg triamcinolone (T20 or T40) and 20 or 40 mg methylprednisolone (M20 or M40) groups; each patient received a single injection of steroid using conventional approach. The four groups were relatively comparable and did not show any significant difference initially in their baseline measurements including pain intensity measured using VAS, pain-free grip strength (PFGS), nerve conduction study (NCS), and two parts of Boston Carpal Tunnel Syndrome Questionnaire: symptom severity scale (SSS) and functional status scale (FSS); the latter was our primary outcome measure. Three months after injection, they were reassessed to evaluate the clinical and electrodiagnostic changes. RESULTS: Almost all NCS parameters, VAS, and PFGS significantly improved after treatment in all the groups (P<0.05). Compound motor action potential amplitude significantly improved only in T40 group (P=0.032), while there was no significant improvement in other groups. Furthermore, SSS remarkably decreased in all the four groups, without any significant difference between the groups (P=0.87). A similar significant decrease was found in FSS, with a higher improvement in T40 group (P=0.009). There was no significant difference between the four groups in other variables after treatment. CONCLUSION: Based on the current data, the efficacy and safety of local injection of triamcinolone and methylprednisolone at doses of 20 and 40 mg were associated with a significant improvement in pain, functional status, and strength. Although, there was no remarkable superiority, 40 mg injection, especially for triamcinolone, yielded better NCS results and functional status.

Nano Packaged Tamoxifen and Curcumin; Effective Formulation against Sensitive and Resistant MCF-7 Cells.

Tamoxifen is routinely used for treatment of Estrogen-positive breast carcinoma. Approximately, 50% of patients with metastatic cancer will develop resistance to Tamoxifen. In this research, Tamoxifen was combined with the anti-cancer compound Curcumin. Diblocknanopolymer was used to package the new formulation of Curcumin and Tamoxifen. Anti-cancer efficacy of the obtained compound was evaluated in Tamoxifen-sensitive (TS). MCF-7, Tamoxifen-resistant (TR) MCF-7 cancer cells and Fibroblast cells. MTT assay was used to evaluate anti-proliferation and toxicity. Flow cytometry and Annexin-V-FLUOS were used to assay anti-proliferation and induction of apoptosis respectively. Our results indicate that the obtained nano-compound is less toxic to normal cells compared to Tamoxifen alone, and has higher anti-proliferation and pro-apoptotic activity on TS-MCF-7 and TR-MCF-7. The nanopolymer reduces the Tamoxifen toxicity in normal cells and counters the developed resistance to the drug in cancer cells.

Preparation and Evaluation of Rifampicin and Co-trimoxazole-loaded Nanocarrier against Brucella melitensis Infection

Background: Brucellosis or Malta fever is a contagious infection common between human and domestic animals. Many antibiotics are used for brucellosis treatment, but they are not efficient and put heavy burden on society. Co-trimoxazole and rifampicin are two candidates for brucellosis treatment. In this study, we aimed to enhance the efficacy of these antibiotics using designed nanoparticles. Methods: Different concentrations of co-trimoxazole and rifampicin were used for loading onto a nanostructure of synthesized monomethoxy poly(ethylene glycol)-oleate (mPEG-OA). The solubility, cytotoxicity, and efficacy of these nano-packed antibiotics on Brucella-infected murine phagocytic cells were examined, as compared with free antibiotics. Then the release nanoparticles was increased approximately 3.5 and 1.5fold, respectively, which is considerable in comparison with free insoluble ones. Results: Despite acceptable loading percentage, the application of co-trimoxazole-loaded nanoparticle on Brucella-infected J774A.1 murine macrophage-like cells did not lead to reduction in the number of bacteria; however, the efficacy of rifampicin on Brucella-infected murine phagocytic cells enhanced. Conclusion: In the current study, the efficacy of rifampicin on reducing the number of Brucella melitensis increased by the novel synthesized nanostructure. In contrast, since co-trimoxazole efficacy did not enhance by loading onto nanoparticles, the co-trimoxazole inefficiency is most likely not due to its low penetration or insolubility, and probably there are other factors that remain to be clarified in the future investigations.

Influence of traffic-related noise and air pollution on self-reported fatigue.

A growing body of evidence suggests that exposure to environmental pollutions is related to health problems. It is, however, questionable whether this condition affects working performance in occupational settings. The aim of this study is to determine the predictive value of age as well as traffic related air and noise pollutions for fatigue. 246 traffic officers participated in this study. Air pollution data were obtained from the local Air Quality Control Company. A sound level meter was used for measuring ambient noise. Fatigue was evaluated by the MFI-20 questionnaire. The general and physical scales showed the highest, while the reduced activity scale showed the lowest level of fatigue. Age had an independent direct effect on reduced activity and physical fatigue. The average of daytime equivalent noise level was between 71.63 and 88.51 dB(A). In the case of high noise exposure, older officers feel more fatigue than younger ones. Exposure to PM10 and O3 resulted in general and physical fatigue. Complex Interactions between SO2, CO and NO2 were found. Exposure to noise and some components of air pollution, especially O3 and PM10, increases fatigue. The authorities should adopt and rigorously implement environmental protection policies in order to protect people.

Dendrosomal curcumin inhibits metastatic potential of human SW480 colon cancer cells through Down-regulation of Claudin1, Zeb1 and Hef1-1 gene expression.

Colon cancer is one of the leading causes of cancer-associated death worldwide. The prognosis for advanced colorectal cancers remains dismal, mainly due to the propensity for metastatic progression. Accordingly, there is a need for effective anti-metastasis therapeutic agents. Since a great body of research has indicated anticancer effects for curcumin, we investigated the effects of dendrosomal curcumin (DNC) on cellular migration and adhesion of human SW480 cells and possible molecular mechanisms involved. Different methods were applied in this study including MTT, Scratch and adhesion assays as well as real-time PCR and transwell chamber assays. Based on the results obtained, DNC inhibits metastasis by decreasing Hef 1, Zeb 1 and Claudin 1 mRNA levels and can reduce SW480 cell proliferation with IC50values of 15.9, 11.6 and 7.64 µM at 24, 48 and 72 h post-treatment. Thus it might be considered as a safe formulation for therapeutic purpose in colorectal cancer cases.

High prevalence of chronic hepatitis B infection among injection drug users in Iran: the need to increase vaccination of adults at risk.

We measured the prevalence of HBV surface antigen (HBsAg) among male injection drug users (IDUs) in Detention, Tehran, Iran. A cross-sectional survey included 499 male IDUs arrested by police during a predetermined police sweep in Tehran (February, 2006). A questionnaire was filled out for each individual. Blood specimens were collected for HBsAg testing. Prevalence of HBsAg was 5.8% (95% CI 3.6-7.9). The majority of chronic HBV infections, 69.2%, were among adults age 25 to 34 years. The high prevalence of HBsAg highlights the need for special efforts to increase vaccination among adult populations at risk for HBV infection in order to reducing continuing transmission and stave off future high burden of disease.

Prevalence and correlates of co-infection with human immunodeficiency virus and hepatitis C virus in male injection drug users in Iran.

OBJECTIVE: Aim of the study was to evaluate the HIV and hepatitis C virus (HCV) coinfection and associated risk behaviors among Injection Drug Users in Detention, Tehran, Iran. METHODS: A cross-sectional survey included 499 male Injection Drug Users arrested by police during a predetermined police sweep in Tehran (February, 2006). At the temporary detention center, they were screened using a urine test and a physical examination for injection marks. Those who were identified as injectors were sent to the rehabilitation center for 3 months. A questionnaire was filled out for each individual by interview. Blood specimens were collected for HIV and HCV testing. The variables associated with HIV/HCV coinfection at a significance level of P<0.10 were considered in multivariate analysis. RESULTS: Of the 417 participants, 100 (24.0%) had HIV/HCV coinfection (95%CI 19.9 - 28.4). Factors independently associated with HIV/HCV coinfection included history of using opioid in jail, and age (P<0.05). There were not any association between other demographic characteristics (marital status, birthplace, residence, and education), type and years of drug abuse, age of first injection, years of injection, sharing needles inside and outside of jail, injection in jail, history of tattooing, any sexual behavior, and history of sexually transmitted diseases with HIV/HCV coinfection (P>0.05). CONCLUSIONS: This study supports that incarceration is contributing to the increased spread of HIV/HCV coinfection. So, there is urgent need for effective harm reduction programs, particularly among incarcerated Injection Drug Users.

Prevalence and correlates of hepatitis C infection among male injection drug users in detention, Tehran, Iran.

For the benefit of planning for the future care and treatment of people infected with hepatitis C virus (HCV) and to help guide prevention and control programs, data are needed on HCV seroprevalence and associated risk factors. We conducted a cross-sectional sero-behavioral survey of injection drug users (IDU) detained for mandatory rehabilitation during a police sweep of Tehran, Iran, in early 2006. During the study period, a consecutive sample comprising 454 of 499 (91.0%) men arrested and determined to be IDU by urine test and physical examination consented to a face-to-face interview and blood collection for HCV antibody testing. Overall, HCV prevalence was 80.0% (95% confidence interval (CI) 76.2-83.6). Factors independently associated with HCV infection included history of incarceration (adjusted OR 4.35, 95% CI 1.88-10.08), age of first injection < or =25 years (OR 2.72, 95% CI 1.09-6.82), and history of tattooing (OR 2.33, 95% CI 1.05-5.17). HCV prevalence in this population of IDU upon intake to jail was extremely high and possibly approaching saturation. Findings support that incarceration is contributing to the increased spread of HCV infection in Iran and calls for urgent increased availability of HCV treatment, long-term preparation for the care of complications of chronic infection, and rapid scale-up of programs for the primary prevention of parenterally transmitted infections among drug users.

HIV seroconversion among injection drug users in detention, Tehran, Iran.

Jails may foster the spread of HIV, particularly among drug users. In 2006, male injection drug users (n = 499) detained in Tehran consented to HIV testing at intake and discharge. HIV prevalence at intake was 24.4%. Nine of those who were HIV negative at intake were positive at discharge (annualized incidence rate 16.8%), including one p24 antigen positive. Jails may be contributing to the rapid spread of HIV in Iran and should be major points for prevention interventions.