Thymoquinone potentiates anti-cancer effects of cisplatin in oral squamous cell carcinoma via targeting oxidative stress.

Recent evidence has proved that thymoquinone as a natural polyphenol has great anticancer and anti-proliferative effects in cancer cells. In this study, we aimed to examine the effects of thymoquinone on increasing cisplatin-induced apoptosis human oral squamous cell carcinoma cells and its underlying molecular mechanisms. SCC-25 cancer cells treated by thymoquinone and cisplatin with different concentrations. Cell viability will determine by using MTT assay. The concentrations of reactive oxygen species (ROS) and antioxidant activities were determined using specific related kits. DNA damage, lipid, and protein oxidation were assessed. Real-time PCR and Western blot analysis will be used to determine the expression of apoptosis-related proteins including Bax, Bcl-2, and caspase-3. Combination of thymoquinone and cisplatin suppressed synergistically SCC-25 cancer cell viability and induced apoptosis in dose-depended manner. Cell treatment with combination of thymoquinone and cisplatin led to accumulation of ROS within cells and increase in the intracellular levels of DNA damage, protein and lipid peroxidation. In addition, the combination of thymoquinone and cisplatin modulated the mRNA and protein expression levels of apoptosis-related proteins including Bax, Bcl-2, and caspase-3. Thymoquinone potentiated cisplatin anti-cancer effect on OSCC by inducing oxidative stress in cells.

The Effect of Berberine Supplementation on Glycemic Control and Inflammatory Biomarkers in Metabolic Disorders: An Umbrella Meta-analysis of Randomized Controlled Trials.

PURPOSE: Several meta-analyses reported berberine (BBR) supplementation improves glycemic parameters and inflammatory marker, but findings remain inconsistent. Therefore, this study was conducted. METHODS: We systematically searched PubMed, Embase, Web of Science, Scopus, and Google Scholar to identify the relevant meta-analyses up to April 2023. FINDINGS: BBR supplementation was effective in reducing fasting blood glucose (FBG) (ESWMD: -0.77; 95% CI: -0.90 to -0.63, and ESSMD: -0.65; 95% CI: -0.83 to -0.47), hemoglobin A1C (HbA1C) (ESWMD: -0.57; 95% CI: -0.68 to -0.46), homeostasis model assessment for insulin resistance (HOMA-IR) (ESWMD: -1.04; 95% CI: -1.66 to -0.42, and ESSMD: -0.71; 95% CI: -0.97 to -0.46), insulin (ESWMD: -1.00; 95% CI: -1.70 to -0.30, and ESSMD: -0.63; 95% CI: -0.94 to -0.32), interleukin (IL)-6 (ESSMD: -1.23; 95% CI: -1.61 to -0.85), tumor necrosis factor-α (TNF-α) (ESSMD: -1.04; 95% CI: -1.28 to -0.79), and C-reactive protein (CRP) (ESWMD: -0.62; 95% CI: -0.74 to -0.50, and ESSMD: -1.70; 95% CI: -2.21 to -1.19). IMPLICATIONS: The finding of our umbrella showed that the supplementation of BBR could be effective in improving glycemic parameters and inflammatory marker in adults.

Mind In Vitro Platforms: Versatile, Scalable, Robust, and Open Solutions to Interfacing with Living Neurons.

Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro-electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built-in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell-derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long-term recording. Overall, this technology, termed "mind in vitro" to underscore the computing inspiration, provides an end-to-end solution that can be widely deployed due to its affordable (>10× cost reduction) and open-source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.

The effect of flaxseed supplementation on sex hormone profile in adults: a systematic review and meta-analysis.

Inconsistent data suggest that flaxseed supplementation may have a role in sex hormones. We aimed to carry out a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating effects of flaxseed supplementation on sex hormone profile. PubMed, Scopus, Embase, Cochrane Library, Web of Science databases, and Google Scholar were searched up to March 2023. Standardized mean difference (SMD) was pooled using a random-effects model. Sensitivity analysis, heterogeneity, and publication bias were reported using standard methods. The quality of each study was evaluated with the revised Cochrane risk-of-bias tool for randomized trials, known as RoB 2. Finding from ten RCTs revealed that flaxseed supplementation had no significant alteration in follicle-stimulating hormone (FSH) (SMD: -0.11; 95% CI: -0.87, 0.66: p = 0.783), sex hormone-binding globulin (SHBG) (SMD: 0.35; 95% CI: -0.02, 0.72; p = 0.063), total testosterone (TT) levels (SMD: 0.17; 95% CI: -0.07, 0.41; p = 0.165), free androgen index (FAI) (SMD = 0.11, 95% CI: -0.61, 0.83; p = 0.759), and dehydroepiandrosterone sulfate (DHEAS) (SMD: 0.08, 95%CI: -0.55, 0.72, p = 0.794). Flaxseed supplementation had no significant effect on sex hormones in adults. Nevertheless, due to the limited included trials, this topic is still open and needs further studies in future RCTs.

The ameliorating effect of limosilactobacillus fermentum and its supernatant postbiotic on cisplatin-induced chronic kidney disease in an animal model.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem affecting millions of people. Probiotics and postbiotics are associated with valuable compounds with antibacterial, anti-inflammatory, and immunomodulatory effects, preserving renal function in CKD patients. The current study is aimed to evaluate the efficacy of Limosilactobacillus fermentum (L. fermentum) and its postbiotic in an animal model of cisplatin-induced CKD. METHODS: The animals were divided into four experimental groups (normal mice, CKD mice with no treatment, CKD mice with probiotic treatment, and CKD mice with postbiotic treatment). CKD mice were induced by a single dose of cisplatin 10 mg/kg, intraperitoneally. For 28 days, the cultured probiotic bacteria and its supernatant (postbiotic) were delivered freshly to the related groups through their daily water. Then, blood urea nitrogen (BUN) and creatinine (Cr) of plasma samples as well as glutathione (GSH), lipid peroxidation, reactive oxygen species, and total antioxidant capacity of kidneys were assessed in the experimental mice groups. In addition, histopathological studies were performed on the kidneys. RESULTS: Application of L. fermentum probiotic, and especially postbiotics, significantly decreased BUN and Cr (P < 0.0001) as well as ROS formation and lipid peroxidation levels (P < 0.0001) along with increased total antioxidant capacity and GSH levels (P < 0.001). The histopathologic images also confirmed their renal protection effect. Interestingly, the postbiotic displayed more effectiveness than the probiotic in some assays. The improvement effect on renal function in the current model is mainly mediated by oxidative stress markers in the renal tissue. CONCLUSIONS: In conclusion, it was found that the administration of L. fermentum probiotic, and particularly its postbiotic in cisplatin-induced CKD mice, showed promising effects and could successfully improve renal function in the animal model of CKD. Therefore, probiotics and postbiotics are considered as probably promising alternative supplements to be used for CKD.

Biosynthesis and Antimicrobial Evaluation of Zinc Oxide Nanoparticles Using Chlorella vulgaris Biomass against Multidrug-Resistant Pathogens.

The rampant increase in antibiotic resistance has created a global barrier to the treatment of multidrug-resistant infections. Biogenic synthesis of nanomaterials is a novel approach to producing nanostructures with biological resources. Algae are known to be clean, nontoxic, cost-beneficial, and environmentally acceptable. Chlorella vulgaris is a popular microalga for its broad applications in food, supplements, pharmaceuticals, and cosmetics. In this study, we used Chlorella vulgaris biomass lyophilized powder as our green resource for the biosynthesis ZnONPs. Chlorella vulgaris culture was harvested at the end of the logarithmic phase, and the biomass was lyophilized. ZnONPs were synthesized using lyophilized biomass and 20 mM zinc acetate dihydrate at a temperature of 70 °C and continuous stirring in a water bath overnight. At the end of the reaction, UV-Vis absorption of colloidal suspension proved the synthesis of ZnONPs. The physicochemical characteristics of nanoparticles were analyzed using FTIR, DLS, TEM, and XRD. Based on FTIR spectra. The antibacterial activity of green synthesized nanostructures was evaluated against methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The synthesized ZnONPs have oxygen-containing groups on the surface that show the synthesized nanoparticles' stabilization. The Zeta potential was -27.4 mV, and the mean particle size was measured as 33.4 nanometers. Biogenic ZnONPs produced in this method have a notable size distribution and excellent surface energy, which can have vast applications like antimicrobial potential in pharmaceuticals as topical forms. Additionally, in order to evaluate the antimicrobial activity of ZnO nanoparticles, we used MRSA and VRE strains and the results showed the anti-MRSA activity at 400 and 625 µg mL-1, respectively. Thus, these biogenic ZnO nanoparticles revealed a substantial antibacterial effect against multidrug-resistant pathogens, associated with several serious systemic infections, and have the potential as an antimicrobial agent for further study.

Recent advances in antiviral effects of probiotics: potential mechanism study in prevention and treatment of SARS-CoV-2.

SARS-CoV-2 is responsible for coronavirus disease 2019 (COVID-19), progressively extended worldwide countries on an epidemic scale. Along with all the drug treatments suggested to date, currently, there are no approved management protocols and treatment regimens for SARS-CoV-2. The unavailability of optimal medication and effective vaccines against SARS-CoV-2 indicates the requirement for alternative therapies. Probiotics are living organisms that deliberate beneficial effects on the host when used sufficiently and in adequate amounts, and fermented food is their rich source. Probiotics affect viruses by antiviral mechanisms and reduce diarrhea and respiratory tract infection. At this point, we comprehensively evaluated the antiviral effects of probiotics and their mechanism with a particular focus on SARS-CoV-2. In this review, we suggested the conceptual and potential mechanisms of probiotics by which they could exhibit antiviral properties against SARS-CoV-2, according to the previous evidence concerning the mechanism of antiviral effects of probiotics. This study reviewed recent studies that speculate about the role of probiotics in the prevention of the SARS-CoV-2-induced cytokine storm through the mechanisms such as induction of anti-inflammatory cytokines (IL-10), downregulation of pro-inflammatory cytokines (TNF-α, IL-2, IL-6), inhibition of JAK signaling pathway, and act as HDAC inhibitor. Also, the recent clinical trials and their outcome have been reviewed. Supplementary Information: The online version contains supplementary material available at 10.1007/s11756-022-01147-y.

The value of thoracic computed tomography scan comparing to reverse transcription-polymerase chain reaction for the diagnosis of COVID-19.

BACKGROUND: Novel coronavirus disease of 2019 (COVID-19) is the current pandemic causing massive morbidity and mortality worldwide. The gold standard diagnostic method in use is reverse transcription-polymerase chain reaction (RT-PCR) which cannot be solely relied upon. Computed tomography (CT) scan is a method currently used for diagnosis of lung disease and can play a substantial role if proved helpful in COVID-19 diagnosis. We conducted this study to evaluate the diagnostic value of CT scan compared to RT-PCR in the diagnosis of COVID-19. MATERIALS AND METHODS: We recruited 291 hospitalized patients suspicious of COVID-19 according to typical clinical findings during February-March 2020. The patients underwent CT-scan and RT-PCR procedures on the day of hospital admission. CT scans were reported by two radiologists as typical, indeterminate, negative, and atypical. Statistical indices were calculated twice: once considering "typical" and "indeterminate" categories as positive and the other time counting "typical" results as positive. RESULTS: The CT reports were classified as typical (64.95%), indeterminate (10.31%), atypical (11%), and negative (13.75%). Considering "typical" and "intermediate" as positive, sensitivity and specificity were 85.3% and 38.8%, respectively, and using the second assumption, the mentioned indices were 75.9% and 50.4%, respectively. CONCLUSION: According to our study, CT results do not create enough diagnostic benefit and could result in incorrect confidence if negative. Since widely available, CT integration in the clinical process may be helpful in screening of suspected patients in epidemics. Yet, suspected patients should be isolated till confirmed by (multiple) PCRs.

Statins as the Controlling Agents for Non-Hodgkin's Lymphomas via Increasing the Casein Kinase 2 Interacting Protein-1: A Hypothesis.

BACKGROUND: Non-Hodgkin's lymphomas (NHL), derived from B- or T-cell, consist of a heterogeneous group of malignant lymphoproliferative disorders. Knockdown of Casein kinase 2 interacting protein-1 (CKIP-1) in NHL promoted cell proliferation and inhibited apoptosis via enhancing phosphorylated Protein Kinase B (PKB or AKT) expression. Statins are the class of drugs that inhibit the ratelimiting step of the mevalonate pathway, which is essential for the biosynthesis of various compounds, including cholesterol. Also, statins have anticancer properties being mediated by different mechanisms. METHODS: A search on databases like Scopus and PubMed with keywords such as statin and non- Hodgkin's lymphomas was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to evaluate and reconfirm the involved cellular signaling pathway. RESULTS: CKIP-1 is involved in the regulation of cell proliferation and apoptosis while plays an important role in many cancers. We can hypothesize that statins may increase the expression levels of CKIP-1 which could contribute to the reductions in phospho-AKT level. Hence, they may ameliorate the NHL patients via suppressing AKT phosphorylation and increasing CKIP- expression. CONCLUSION: Present review confirms the positive effect of statins on NHL by increasing CKIP-1 and reducing cell proliferation, subsequently.

Reference values of nuchal fold thickness in an Iranian population sample.

BACKGROUND: Considering that ethnicity and gestational age (GA) could affect the value of nuchal fold thickness (NFT) in mid-trimester, we aimed to determine the reference intervals of NFT values for each gestational week from 16 to 24 weeks of pregnancy among a group of Iranian pregnant women. MATERIALS AND METHODS: In this cross-sectional study, medical files of pregnant women who underwent fetal anomaly scanning at 16-24 weeks of gestation were reviewed and the following data were extracted: GA, value of NFT, value of nuchal translucency (NT) in their previous ultrasound study, if available, and head circumference (HC). The 5th, 25th, 50th, 75th, and 95th percentiles of NFT for each gestational week were determined. The association between NFT and HC, GA, and NT were also determined. RESULTS: Medical files of 882 pregnant women were studied. The expected 95th percentile value of NFT between 16th and 24th weeks of gestation ranged from 4 mm to 5.9 mm. The mean (standard deviation) of NFT increased with GA from 2.67 (0.90) mm at 16th weeks to 4.69 (0.71) mm at 24th weeks. There was a significant positive association between NFT and GA (ß = 1.11, p < 0.001), HC (ß = 0.21, p < 0.001), and NT (ß = 0.351, p < 0.001). CONCLUSION: The findings of this study revealed that before the 20th week of gestation, the appropriate cutoff value of NFT is 5 mm, and for 21st to 24th weeks, the proper cutoff is 6 mm. However, for providing more conclusive results, further studies with larger sample size and considering the impact of other influencing variables are recommended.

Assessment of blunt splenic trauma: Which imaging scoring system is superior?

BACKGROUND: Spleen is the most common viscera that may be hurt in blunt abdominal trauma. Operative or nonoperative management of splenic injury is a dilemma. The American Association for the Surgery of Trauma (AAST) is the most common grading system which has been used for the management of blunt splenic injuries. The new recommended grading system assesses other aspects of splenic injury such as contrast extravasation, pseudoaneurysm, arteriovenous fistula, and severity of hemoperitoneum, as well. The aim of this study is to compare and prioritize the cutoff of AAST grading system with the new recommended one. MATERIALS AND METHODS: This is a cross-sectional study on patients with splenic injury caused by abdominal blunt trauma referred to Isfahan University of Medical Sciences affiliated Hospitals, Iran, in 2013-2016. All patients underwent abdominopelvic computed tomography scanning with intravenous (IV) contrast. All images were reported by a single expert radiologist, and splenic injury grading was reported based on AAST and the new recommended system. Then, all patients were followed to see if they needed surgical or nonsurgical management. RESULTS: Based on the findings of this study conducted on 68 patients, cutoff point of Grade 2, in AAST system, had 90.3% (95% confidence interval [CI]: 0.73-0.97) specificity, 51.4% (95% CI: 0.34-0.67) sensitivity, 86.4% (95% CI: 0.64-0.95) positive predictive value (PPV), and 60.9% (95% CI: 0.45-0.74) negative predictive value (NPV) for prediction of surgical management requirement, while it was 90.3% (95% CI: 0.73-0.97) specificity, 45.9% (95% CI: 0.29-0.63) sensitivity, 85% (95% CI: 0.61-0.96) PPV, and 58.3% (95% CI: 0.43-0.72) NPV for the new system (P = 0.816). CONCLUSION: In contrast to the previous studies, the new splenic injury grading method was not superior to AAST. Further studies with larger populations are recommended.

Breast cancer screening: Evidence of the effect of adjunct ultrasound screening in women with unilateral mammography-negative dense breasts.

BACKGROUND: Patients with the previous history of breast cancer are in risk of contralateral breast cancer. On the other hand, increased breast density is a risk factor for breast cancer and the sensitivity of detecting nonpalpable cancers in screening mammography in radiographically dense breasts is low. The use of ultrasonography in dense breast remains a controversial topic. The purpose of this study was to assess the usefulness of routine ultrasonography in follow-up of women with the previous history of breast cancer and negative mammography but dense breasts. MATERIALS AND METHODS: In a cross-sectional study, a total of 267 individuals with unilateral postmastectomy mammogram screened and 153 subjects assigned to study. There were 28 subjects with American College of Radiology (ACR) breast density 2 and 125 with ACR breast density 3-4, which there was no new finding in their mammogram in comparison to previous studies. We assumed subjects with ACR breast density 3-4 as mammographic Breast Imaging Reporting and Data System (BI-RADS) category 0 for malignancy. Standard two-view mammogram was performed for all participants, and breast ultrasound (US) examinations were performed by an expert radiologist in radial and anti-radial planes. The data were analyzed using SPSS version 20.0 (SPSS Inc., Chicago, Illinois, USA). RESULTS: The results showed that in subjects with ACR breast density 3-4, when there was no new density in two consecutive mammograms in comparison to previous studies, US also showed no possibility for malignancy (BI-RADS 1-2). And also in subjects with ACR breast density 2, when the mammographic results were BI-RADS 1-2, the US results was the same. CONCLUSION: Our data indicate that for the detection of breast cancer, sensitivity of US was not greater than mammography in patients with postmastectomy unilateral dense breast if there is not any new density.

Normal reference range of fetal nuchal translucency thickness in pregnant women in the first trimester, one center study.

BACKGROUND: Considering that establishment of reference value of nuchal translucency (NT)-related to the crown rump length (CRL) during the first trimester will be helpful for determining an appropriate cutoff level for screening of increased NT thickness-related abnormalities, we determined the NT thickness and investigated its relation with different chromosomal and nonchromosomal abnormalities among a large sample size of pregnant Iranian women. MATERIALS AND METHODS: In this analytic cross-sectional study, pregnant women who were in their first trimester were enrolled at their antenatal visit. Using an abdominal ultrasonography, the fetal NT thickness of the studied population was measured. Those with increased NT thickness were determined. The reference value of NT thickness (5th, 25th, 50th, 75th, and 95th percentiles) within each 5-mm range of CRL and during the 11th, 12th, and 13th gestational weeks were determined. The presences of the different chromosomal and nonchromosomal abnormalities were compared in women with different percentiles of NT thickness who underwent amniocentesis and those who did not. RESULTS: 1,614 pregnant women were evaluated. The mean NT thickness was 1.30 ± 0.54 mm. Increased NT thickness >2 mm and >95th percentile according to their gestational age (GA) was detected in 89 (5.5%) and 58 (3.6%) pregnant women. The reference 95th percentile value range for NT was 1.8-2.35 and increased NT thickness according to our obtained values was associated significantly with chromosomal abnormalities. CONCLUSION: The obtained reference range in our studied population was different from that reported for other ethnic groups and it is suggested that using this values are more favorable for screening of chromosomal abnormalities during the first trimester of pregnancy than the recommended single cutoff value.