Identification of important symptoms and diagnostic hypothyroidism patients using machine learning algorithms.

Background: Hypothyroidism is one of the most common endocrine diseases. It is, however, usually challenging for physicians to diagnose due to nonspecific symptoms. The usual procedure for diagnosis of Hypothyroidism is a blood test. In recent years, machine learning algorithms have proved to be powerful tools in medicine due to their diagnostic accuracy. In this study, the authors aim to predict and identify the most important symptoms of Hypothyroidism using machine learning algorithms. Method: In this cross-sectional, single-center study, 1296 individuals who visited an endocrinologist for the first time with symptoms of Hypothyroidism were studied, 676 of whom were identified as patients through thyroid-stimulating hormone testing. The outcome was binary (with Hypothyroidism /without Hypothyroidism). In a comparative analysis, random forest, decision tree, and logistic regression methods were used to diagnose primary Hypothyroidism. Results: Symptoms such as tiredness, unusual cold feeling, yellow skin (jaundice), cold hands and feet, numbness of hands, loss of appetite, and weight Hypothyroidism gain were recognized as the most important symptoms in identifying Hypothyroidism. Among the studied algorithms, random forest had the best performance in identifying these symptoms (accuracy=0.83, kappa=0.46, sensitivity=0.88, specificity=0.88). Conclusions: The findings suggest that machine learning methods can identify Hypothyroidism patients who show relatively simple symptoms with acceptable accuracy without the need for a blood test. Greater familiarity and utilization of such methods by physicians may, therefore, reduce the expense and stress burden of clinical testing.

Prevalence of metabolically healthy obesity and healthy overweight and the associated factors in southern Iran: A population-based cross-sectional study.

Background and Aims: Obesity is considered a major growing threat to public health which could negatively affect the quality of life. The current cross-sectional study was conducted to investigate the population-based prevalence of metabolically healthy obesity (MHO) and healthy overweight (MHOW) and associated factors in southern Iran. Methods: Baseline data from the Pars Cohort Study was analyzed. Metabolically healthy participants were identified based on the definition of the American Heart Association for the metabolic syndrome. The prevalence of MHOW and MHO and their 95% confidence intervals were estimated. Poisson regression was applied for the calculation of prevalence ratios (PRs). Results: Gender- and age-standardized prevalences of MHOW and MHO were 6.3% (6.0%-6.6%) and 2.3% (2.1%-2.5%), respectively. The following factors were associated with being MHOW compared with those with normal weight: Being younger, female gender (1.31, 1.20-1.43), higher socioeconomic status, being noncurrent cigarette smoker (1.27, 1.11-1.45), low level of physical activity (1.14, 1.03-1.25), having normal overweight during adolescence, and overweight (1.35, 1.24-1.48) or obesity (1.68, 1.53-1.86) during young adulthood. We also found strong associations between MHO and younger age groups, female gender (2.87, 2.40-3.42), being married (1.57, 1.08-2.27), Fars ethnicity (1.25, 1.10-1.43), higher socioeconomic status, ever use of tobacco (1.14, 1.00-1.30), never use of opium (1.85, 1.19-2.86), lower physical activity (1.45, 1.20-1.72), being normal weight in 15-year body pictogram and being overweight (1.87, 1.59-2.20) or obese (3.20, 2.74-3.72) in 30-year body pictogram when considering those with normal weight or MHO. Conclusion: Potentially modifiable factors including physical activity should be more emphasized. Furthermore, our study issued that it would be more reasonable that the prevention of unhealthy obesity be initiated before the development of MHO, where there are more protective factors and they could be more effective.

Exploring the impact of stage and tumor site on colorectal cancer survival: Bayesian survival modeling.

Colorectal cancer is a prevalent malignancy with global significance. This retrospective study aimed to investigate the influence of stage and tumor site on survival outcomes in 284 colorectal cancer patients diagnosed between 2001 and 2017. Patients were categorized into four groups based on tumor site (colon and rectum) and disease stage (early stage and advanced stage). Demographic characteristics, treatment modalities, and survival outcomes were recorded. Bayesian survival modeling was performed using semi-competing risks illness-death models with an accelerated failure time (AFT) approach, utilizing R 4.1 software. Results demonstrated significantly higher time ratios for disease recurrence (TR = 1.712, 95% CI 1.489-2.197), mortality without recurrence (TR = 1.933, 1.480-2.510), and mortality after recurrence (TR = 1.847, 1.147-2.178) in early-stage colon cancer compared to early-stage rectal cancer. Furthermore, patients with advanced-stage rectal cancer exhibited shorter survival times for disease recurrence than patients with early-stage colon cancer. The interaction effect between the disease site and cancer stage was not significant. These findings, derived from the optimal Bayesian log-normal model for terminal and non-terminal events, highlight the importance of early detection and effective management strategies for colon cancer. Early-stage colon cancer demonstrated improved survival rates for disease recurrence, mortality without recurrence, and mortality after recurrence compared to other stages. Early intervention and comprehensive care are crucial to enhance prognosis and minimize adverse events in colon cancer patients.

Polypharmacy and pattern of medication use among patients with gastroesophageal reflux disease: results from Pars Cohort study.

BACKGROUND: Gastroesophageal Reflux Disease (GERD) is a common chronic condition. Its chronic nature may affect the pattern of medication use. This study aimed to investigate the prevalence, associated factors, and patterns of polypharmacy and medication use among GERD patients in southwestern Iran. METHODS: We used data from the Pars Cohort Study. We classified drugs using the Anatomical Therapeutic Chemical classification system. The Lexicomp® database was used to assess potential drug-drug interactions. Multivariable Poisson regression was applied. Adjusted prevalence ratio (PR) and its 95% confidence interval (CI) were estimated. RESULTS: A total of 9262 participants were included. Among 2,325 patients with GERD, age-standardized prevalence of polypharmacy was 9.5% (95% CI: 7.5%, 11.6%) in males, and 19.3% (95% CI: 17.2%, 21.4%) in females. The PR of experiencing Polypharmacy by GERD patients compared to non-GERD patients was 1.82 (95% CI: 1.61, 2.05%). Multimorbidity (PR: 3.33; CI: 2.66, 4.15), gender (PR: 1.68; CI: 1.30, 2.18), and metabolic syndrome (PR: 1.77; CI: 1.45, 2.15) were associated with polypharmacy among GERD patients. Drugs for acid-related disorders were the most common used drugs among men, women and elders. We found that 13.9%, 4.2%, and 1.1% of GERD patients had type C, D and X drug interactions, respectively. CONCLUSION: GERD is correlated with a higher prevalence of polypharmacy. Among GERD patients, females, those with multi-morbidities, and those with metabolic syndrome may be affected more by polypharmacy. Considering the fairly high rate of interactions identified, a review of the medication list is essential when approaching GERD patients, and physicians must check for medications that may worsen GERD.

The Association of Methylation Status and Expression Level of MyoD1 with DNMT1 Expression Level in Breast Cancer Patients.

Background: Breast cancer (BC) is the most common malignancy in women worldwide. The methylation status of MyoD1, a tumor suppressor gene, is enrolled in various cancers, i.e., BC. Various studies showed the impact of MyoD1 epigenetic dysregulation in BC. This study aimed to investigate the methylation status and expression level of MyoD1 in BC patients and its association with the expression of DNMT1. Materials and Methods: This case-control study was conducted on 30 cases (pathology-confirmed ductal carcinoma) and 18 controls (fibroadenoma and fibrocystic masses), referred to Velayat Hospital, Qazvin, Iran. The expression of the MyoD1 and DNMT1 and the promoter methylation of the MyoD1 were evaluated in tissue blocks of BC patient masses using qRT-PCR and MS-PCR assays, respectively. SPSS 24.0 was used to analyze the data. Results: The MyoD1 promoter is hypermethylated in BC patients compared to controls (p =0.001). The expression level of MyoD1 in BC patients was significantly reduced compared to controls (fold change =0.13, p =0.042). In addition, in BC patients, the reduced expression level of MyoD1 was significantly associated with methylation of the MyoD1 promoter (p =0.001). There is no significant difference between the expression level of DNMT1 in BC patients and controls (p =0.197). A significant association is found between the expression of DNMT1 and the methylation status of the MyoD1 promoter (p =0.038). Discussion: The expression level of MyoD1 is affected by the methylation status of the promoter of this gene. Moreover, the expression level and methylation status of MyoD1 are correlated with clinical parameters.

Cobalt ferrite nanoparticle for the elimination of CD133+CD44+ and CD44+CD24-, in breast and skin cancer stem cells, using non-ionizing treatments.

Background: Cancer stem cells (CSCs) are the most challenging issue in cancer treatment, because of their high resistance mechanisms, that can cause tumor recurrence after common cancer treatments such as drug and radiation based therapies, and the insufficient efficiency of common treatments in CSCs removal and the recurrence of tumors after these treatments, it is essential to consider other methods, including non-ionizing treatments likes light-based treatments and magnetic hyperthermia (MHT). Method and material: After synthesis, characterization and investigation, the toxicity of novel on A375 and MAD-MB-231 cell lines, magnetic hyperthermia and light-based treatments were applied. MTT assay and flow cytometry was employed to determine cell survival. the influence of combination therapy on CD44 + CD24-and CD133 + CD44+ cell population, Comparison and evaluation of combination treatments was done respectively using Combination Indices (CIs). Result: The final nanoparticle has a high efficiency in producing hydroxyl radicals and generating heat in MHT. According to CIs, we can conclude that combined using of light-based treatment and MHT in the presence of final synthesized nanoparticle have synergistic effect and a high ability to reduce the population of stem cells in both cell lines compared to single treatments. Conclusion: In this study a novel multi-functional nanoplatform acted well in dual and triple combined treatments, and showed a good performance in the eradication of CSCs, in A375 and MAD-MB-231 cell lines.

Prevalence and Correlates of Polypharmacy, and Drug Utilization Pattern in a Semi-urban Population: Results from the Pars Cohort Study.

BACKGROUND: Although polypharmacy is considered a major predictor of irrational use of drugs, little is known about polypharmacy in developing regions. We aimed to indicate the prevalence and correlates of polypharmacy and to determine the medication profile at the population level in southern Iran. METHODS: In this cross-sectional study, we analyzed data from participants of the Pars Cohort Study (PCS) (aged above 40 years, N=9269). Polypharmacy was defined as using five or more medications concurrently. A Poisson multivariable model was applied to estimate the adjusted prevalence ratios (APRs) of various risk factors. The Anatomical Therapeutic Chemical (ATC) classification system was used for classifying medications. RESULTS: Prevalence of polypharmacy was 10.4%, (95% CI: 9.75; 11.08) and it was higher among females (15.0%), older adults (age≥65 years) (16.0%), and individuals with more than two chronic conditions (31%). Being female, educated, married, and not having a low socio-economic class were independently associated with a higher likelihood of polypharmacy. The most prevalent medications among female participants were sex hormones and modulators of the genital system (58.4%), drugs for acid-related disorders (14.6%), and anti-anemic preparations (13.6%,). On the other hand, males were using acid-related disorders (14.6%), anti-inflammatory and anti-rheumatic products (7.8%), and beta-blocking agents (6.3%). CONCLUSION: The prevalence of polypharmacy in our sample was relatively low, especially among males. Cardiovascular drugs, acid suppressants, hormonal contraceptives, and anti-anemic preparations are drug classes with the highest contribution to polypharmacy.

Coenzyme Q10 and Its Therapeutic Potencies Against COVID-19 and Other Similar Infections: A Molecular Review.

Purpose: New lethal coronavirus disease 2019 (COVID-19), currently, has been converted to a disastrous pandemic worldwide. As there has been found no definitive treatment for the infection in this review we focused on molecular aspects of coenzyme Q10 (CoQ10) and possible therapeutic potencies of CoQ10 against COVID-19 and similar infections. Methods: This is a narrative review in which we used some authentic resources including PubMed, ISI, Scopus, Science Direct, Cochrane, and some preprint databases, the molecular aspects of CoQ10 effects, regarding to the COVID-19 pathogenesis, have been analyzed and discussed. Results: CoQ10 is an essential cofactor in the electron transport chain of the phosphorylative oxidation system. It is a powerful lipophilic antioxidant, anti-apoptotic, immunomodulatory and anti-inflammatory supplement which has been tested for the management and prevention of a variety of diseases particularly diseases with inflammatory pathogenesis. CoQ10 is a strong anti-inflammatory agent which can reduce tumor necrosis factor-α (TNF-α), interleukin (IL)- 6, C-reactive protein (CRP), and other inflammatory cytokines. The cardio-protective role of CoQ10 in improving viral myocarditis and drug induced cardiotoxicity has been determined in different studies. CoQ10 could also improve the interference in the RAS system caused by COVID-19 through exerting anti-Angiotensin II effects and decreasing oxidative stress. CoQ10 passes easily through blood-brain barrier (BBB). As a neuroprotective agent CoQ10 can reduce oxidative stress and modulate the immunologic reactions. These properties may help to reduce CNS inflammation and prevent BBB damage and neuronal apoptosis in COVID-19 patients. Conclusion: CoQ10 supplementation may prevent the COVID-19-induced morbidities with a potential protective role against the deleterious consequences of the disease, further clinical evaluations are encouraged.

Polypill protects MAFLD patients from cardiovascular events and mortality: a prospective trial.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel term that distinguishes patients at risk of adverse clinical outcomes with higher accuracy than those with non-alcoholic fatty liver disease (NAFLD). Cardiovascular mortality is the leading cause of death in MAFLD. The current literature lacks large-scale prospective studies that address preventive approaches for cardiovascular health in MAFLD. We investigated whether MAFLD patients benefit from a fixed-dose combination therapy (Aspirin, hydrochlorothiazide, atorvastatin, valsartan), known as a Polypill. METHODS: Analysis was performed (stratified based on MAFLD status) of a clinical trial that included 1596 individuals randomly allocated to an intervention (polypill) or a control (usual care) group. Patients were followed up for five years for any adverse drug reaction, major cardiovascular events, and mortality. Univariable and multivariable survival analyses were performed, and the interaction level was assessed by R programming. RESULTS: Patients who consumed the polypill had significantly lower hazard ratios of major cardiovascular events incidence (HR 0.56, 95% CI 0.41-0.78) and cardiovascular mortality (HR 0.41, 95% CI 0.2-0.86) compared to the control group. Polypill showed significantly better results in lowering cardiovascular events in MAFLD patients than in the general population. (p-value for interaction: 0.028). Moreover, comparing those patients who had high adherence to the Polypill, with the control group, further enhanced the results. CONCLUSIONS: Major cardiovascular events are prevented in MAFLD patients who consume the Polypill. MAFLD patients benefit from the Polypill more than the general population.

The Impact of Obesity Surgery on Serum Uric Acid in People With Severe Obesity: A Retrospective Study.

Studies indicate an association between hyperuricemia (HUA) and metabolic syndrome risk factors. On the other hand, obesity is a major modifiable and independent risk factor for HUA and gout. However, evidence concerning the effects of bariatric surgery on serum uric acid levels is limited and not completely clarified. This retrospective study was carried out with 41 patients who underwent sleeve gastrectomy (n = 26) and Roux-en-Y gastric bypass (n = 15) from September 2019 to October 2021. Anthropometric, clinical, and biochemical data, including uric acid blood urea nitrogen and creatinine fasting blood sugar (FBS), serum triglyceride (TG), and serum cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), were measured preoperatively and postoperative 3, 6 and 12 months. From baseline to 6 and 12 months, bariatric surgery resulted in a significant decrease in serum uric acid of patients with severe obesity (p < 0.001). The decreases in serum FBS, TG, and cholesterol of patients were significant during 6 and 12 months of follow-up (p < 0.05). However, the HDL increase of patients was not statistically significant in 6 and 12 months (p > 0.05). Besides, although patients' serum level of LDL decreased significantly during the 6 months of follow-up (p = 0.007), it was not significant after 12 months (p = 0.092). Bariatric surgery significantly reduces serum uric acid levels. Therefore, it may be an effective supplementary therapy for lowering serum uric acid concentrations in morbidly obese patients.

Nanotechnology-based diagnostics and therapeutics in acute lymphoblastic leukemia: a systematic review of preclinical studies.

Background: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and release drugs selectively at desired sites using targeting or sensing strategies. As drug carriers, they could improve therapeutic outcomes while reducing systemic toxicity. They have also shown promise in improving leukemia detection and diagnosis. The study aimed to assess the potential of nanotechnology-based diagnostics and therapeutics in preclinical human acute lymphoblastic leukemia (h-ALL). Methods: We performed a systematic search through April 2022. Articles written in English reporting the toxicity, efficacy, and safety of nanotechnology-based drugs (in the aspect of treatment) and specificity, limit of detection (LOD), or sensitivity (in the aspect of the detection field) in preclinical h-ALL were included. The study was performed according to PRISMA instructions. The methodological quality was assessed using the QualSyst tool. Results: A total of 63 original articles evaluating nanotechnology-based therapeutics and 35 original studies evaluating nanotechnology-based diagnostics were included in this review. As therapeutics in ALL, nanomaterials offer controlled release, targeting or sensing ligands, targeted gene therapy, photodynamic therapy and photothermic therapy, and reversal of multidrug-resistant ALL. A narrative synthesis of studies revealed that nanoparticles improve the ratio of efficacy to the toxicity of anti-leukemic drugs. They have also been developed as a vehicle for biomolecules (such as antibodies) that can help detect and monitor leukemic biomarkers. Therefore, nanomaterials can help with early diagnostics and personalized treatment of ALL. Conclusion: This review discussed nanotechnology-based preclinical strategies to achieve ALL diagnosis and therapy advancement. This involves modern drug delivery apparatuses and detection devices for prompt and targeted disease diagnostics. Nonetheless, we are yet in the experimental phase and investigational stage in the field of nanomedicine, with many features remained to be discovered as well as numerous problems to be solved.

Fluorescence anisotropy cytosensing of folate receptor positive tumor cells using 3D polyurethane-GO-foams modified with folic acid: molecular dynamics and in vitro studies.

Integrated polyurethane (PU)-based foams modified with PEGylated graphene oxide and folic acid (PU@GO-PEG-FA) were developed with the goal of capturing and detecting tumor cells with precision. The detection of the modified PU@GO-PEG surface through FA against folate receptor-overexpressed tumor cells is the basis for tumor cell capture. Molecular dynamics (MD) simulations were applied to study the strength of FA interactions with the folate receptor. Based on the obtained results, the folate receptor has intense interactions with FA, which leads to the reduction in the FA interactions with PEG, and so decreases the fluorescence intensity of the biosensor. The synergistic interactions offer the FA-modified foams a high efficiency for capturing the tumor cell. Using a turn-off fluorescence technique based on the complicated interaction of FA-folate receptor generated by target recognition, the enhanced capture tumor cells could be directly read out at excitation-emission wavelengths of 380-450 nm. The working range is between 1×10 2 to 2×10 4 cells mL -1 with a detection limit of 25 cells mL -1 and good reproducibility with relative standard deviation of 2.35%. Overall, findings demonstrate that the fluorescence-based biosensor has a significant advantage for early tumor cell diagnosis.

The multimodal effect of Photothermal/Photodynamic/Chemo therapies mediated by Au-CoFe2O4 @Spiky nanostructure adjacent to mitoxantrone on breast cancer cells.

BACKGROUND: Conventional cancer treatments are associated with a number of limitations, including non-selectivity, toxicity and multidrug resistance, so new nanotechnologies are being developed forcancer diagnosis and therapy. Phototherapy approach based on nanotechnology is a hopeful strategy to overcome these problems. Photothermal (PTT) and photodynamic therapies (PDT), in addition to having non-invasive properties, are known as promising methods for treatment of tumors. In this study, CoFe2O4 theranostic magnetic nanoparticles coated with spiky gold nanoparticles were designed and synthesized and its photothermal effects were evaluated in combination with the photodynamic and chemotherapeutic effects of mitoxantrone (MTX) under in vitro conditions. METHODS AND MATERIALS: At first, CoFe2O4 @Spiky Au nanostructure was synthesized and after its characterization, cytotoxicity of MTX, CoFe2O4 @ Spiky Au (MGNS) and CoFe2O4 @ Au were determined on MDA-MB-231 cell line. Then, the concentrations required for inducing 50% cell death (IC50) and appropriate concentration for this study was obtained. Cells were irradiated by an 808 nm laser and a non-synchronous light source at 670 nm at the separate groups. The viability of treated cells was determined via MTT test 48 h after treatment. RESULTS: In the groups receiving energy density (5-40) J/cm2, at the lower laser dose an increase in cell survival was observed (P < 0.05) and then cell survival was decreased (P < 0.05). In the groups receiving non-coherent light (2-18 J/cm2) from the beginning, a decreasing trend in cell survival is observed. CONCLUSION: The overlap of the emission spectrum of the light source and the absorption spectrum of the nanostructure amplified the cell death. Similar to the Hormesis model reported for ionizing radiation effects, at low light doses with the bio-phasic response dose model, increased cell survival and proliferation can be expected.

Thymus vulgaris, a natural pharmacy against COVID-19: A molecular review.

Introduction: A worldwide pandemic infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a deadly disease called COVID-19. Interaction of the virus and the Angiotensin converting-enzyme 2 (ACE2) receptor leads to an inflammatory-induced tissue damage. Thymus vulgaris L. (TvL) is a plant with a long history in traditional medicine that has antimicrobial, antiseptic, and antiviral properties. Thymol and Carvacrol are two important biological components in Thyme that have anti-inflammatory, antioxidant, and immunomodulatory properties. This study is a molecular review on the potential effects of TvL and its active compounds on SARS-COV2 infection. Method: This is a narrative review in which using PubMed, Scopus, ISI, Cochrane, ScienceDirect, Google scholar, and Arxiv preprint databases, the molecular mechanisms of therapeutic and protective effects of TvL and its active compounds have been discussed regarding the molecular pathogenesis in COVID-19. Results: Thyme could suppress TNF-alpha, IL-6, and other inflammatory cytokines. It also enhances the anti-inflammatory cytokines like TGF-beta and IL-10. Thyme extract acts also as an inhibitor of cytokines IL-1-beta and IL-8, at both mRNA and protein levels. Thymol may also control the progression of neuro-inflammation toward neurological disease by reducing some factors. Thyme and its active ingredients, especially Thymol and Carvacrol, have also positive effects on the renin-angiotensin system (RAS) and intestinal microbiota. Conclusions: Accordingly, TvL and its bioactive components may prevent COVID-19 complications and has a potential protective role against the deleterious consequences of the disease.

Population-based pattern of medication use and prevalence of polypharmacy among patients with cardiovascular diseases: results of the Pars cohort study from Iran.

BACKGROUND: Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran. METHOD: We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated. RESULTS: Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57-4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07-2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00-1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30-1.53), high physical activity (PR: 0.66; 95% CI 0.45-0.95), use of opiate ever (PR: 0.46; 95% CI 0.26-0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12-0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs. CONCLUSION: Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial.

Graphene-MoS2 polyfunctional hybrid hydrogels for the healing of transected Achilles tendon.

Healing of injured tendon is a major clinical challenge in orthopaedic medicine, due to the poor regenerative potential of this tissue. Two-dimensional nanomaterials, as versatile scaffolds, have shown a great potential to support, trigger and accelerate the tendon regeneration. However, weak mechanical properties, poor functionality and low biocompatibility of these scaffolds as well as post-surgery infections are main drawbacks that limit their development in the higher clinical phases. In this work, a series of hydrogels consisting polyglycerol functionalized reduced graphene oxide (PG), polyglycerol-functionalized molybdenum disulfide (PMoS2) and PG/PMoS2 hybrid within the gelatin matrix are formulated in new scaffolds and their ability for the healing of injured Achilles tendon, due to their high mechanical properties, low toxicity, cell proliferation enhancement, and antibacterial activities is investigated. While scaffolds containing PG and PMoS2 showed a moderate tendon regeneration and anti-inflammatory effect, respectively, their hybridization into PG/PMoS2 demonstrated a synergistic healing efficiency. Along the same line, an accelerated return of tendon function with low peritendinous adhesion and low cross-sectional area in animal group treated with scaffold containing PG/PMoS2 was observed. Taking advantage of the high biocompatibility, high strength, straightforward construction and fast tendon regeneration, PG/PMoS2 can be used as a new scaffold for the future tissue engineering.

A Novel Anti-CD22 scFv.Bim Fusion Protein Effectively Induces Apoptosis in Malignant B cells and Promotes Cytotoxicity.

CD22 is a B-cell surface antigen which is highly expressed in cancerous B-cell lineages. Anti-CD22 antibodies are currently under focus as promising biologics against hematologic B-cell malignancies. Herein, we introduce a novel active recombinant anti-CD22 scFv.Bim fusion protein for targeting this cancerous antigen. An expression cassette encoding anti-CD22 scFv.Bim fusion protein was expressed in Pichia pastoris. The binding ability, cytotoxicity, and apoptotic activity of the purified recombinant protein against CD22+ Raji cell line were assessed by flow cytometry, microscopy, and MTT assay. Using bioinformatics, the 3D structure of the fusion protein and its interaction with CD22 were assessed. The in vitro binding analysis by immunofluorescence microscopy and flow cytometry demonstrated the specific binding of scFv.Bim to CD22+ Raji cells but not to CD22- Jurkat cells. MTT data and Annexin V/PI flow cytometry analysis confirmed the apoptotic activity of anti-CD22 scFv.Bim against Raji cells but not Jurkat cells. In silico analysis also revealed the satisfactory stereochemical quality of the 3D model and molecular interactions toward CD22. This novel recombinant anti-CD22 scFv.Bim fusion protein could successfully deliver the pro-apoptotic peptide, BIM, to the target cells and thus nominates it as a promising molecule in treating B-cell malignancies.

Population-based prevalence of polypharmacy and patterns of medication use in southwestern Iran: A cross-sectional study.

BACKGROUND: Pharmaceutical medications are considered an important component of healthcare delivery and there is a need for its rational use; although there have been major improvements in the pharmaceutical sector in the recent past, inappropriate medication use is considered a major threat to patients' health. Therefore, the pattern of medication use should be monitored routinely. The aim of this study was to investigate the population-based prevalence of polypharmacy and the patterns of medication use in southwestern Iran. We also investigated correlates between polypharmacy and patterns of medication use. METHODS: Data from the Khuzestan Comprehensive Health Study (KCHS) which consists information of 30 506 with age range to 20 to 65 years were used. Crude and age-standardized prevalence of polypharmacy and their 95% confidence intervals were estimated for different subpopulations. Multivariable Poisson regression modeling was applied, and adjusted prevalence ratios and their 95% confidence intervals were estimated. The Anatomical Therapeutic Chemical classification system (first and second levels) was used for drug classification in different groups based on age, gender, and socioeconomic status. RESULTS: Out of 30 506 adults, 93.3% were not on any medications, and age- and gender-standardized prevalence of polypharmacy was 0.24%. The lowest estimated prevalence was among Arab participants (0.13%). The prevalence of polypharmacy was 1.57% among elderly people, and 4.78% among patients with heart diseases. Socioeconomic status was not associated with polypharmacy (prevalence ratio: 0.95; p = 0.573) but was significantly associated with patterns of medications use for alimentary tract and metabolism and nervous system diseases. The most common drug classes were cardiovascular system (3.93%), alimentary tract and metabolism (2.79%), nervous system (1.01%), systemic hormonal preparations (0.69%), and blood and blood-forming organs (0.38%). CONCLUSIONS: The prevalence of polypharmacy is very low in Khuzestan province, especially in the Arab population. Future research is needed to investigate the causes of medication underuse in this population.

Anemia prevalence, severity, types, and correlates among adult women and men in a multiethnic Iranian population: the Khuzestan Comprehensive Health Study (KCHS).

BACKGROUND: Despite all recent health-related improvements, anemia remains an extensive global public health issue affecting the lives of about one-fourth of the world population in a geographically heterogeneous pattern. We, therefore, aimed to illustrate the prevalence, severity, most common types, and major determinants of anemia among adults in Khuzestan, Iran, from 2016 to 2019. METHODS: In a large population-based cross-sectional study comprising of a diverse population, each participant underwent a questionnaire-based interview and laboratory testing for hematological analysis. A hemoglobin (HGB) concentration of < 12 g/dL in non-pregnant women and < 13 g/dL in men were defined anemic. The multivariate logistic regression analysis was performed to explore the association between anemia and its potential determinants. RESULTS: Data on 29,550 (96.87%) males and non-pregnant females between 20-65 years of age (mean age: 41.90 ± 11.88 years; female sex: 63.58%; Arab ethnicity: 48.65%), whose HGB level was available, were included in the study. The mean ± SD HGB concentration was 13.75 ± 1.65 g/dL. The age- and sex-standardized prevalence rate of anemia was 10.86% (95% CI: 10.51-11.23%). The most prevalent degree was mild anemia (7.71%, 95% CI: 7.40-8.03%) and only 0.17% were severely anemic. Of those considered anemic, the highest proportion was related to normochromic/microcytic (50.65%), followed by hypochromic/microcytic (30.29%). In the multiple logistic regression, the parameters of female gender (OR: 3.17, 95% CI: 2.68-3.76), age group of 35-49 years (OR: 1.66, 95% CI: 1.52-1.82), being underweight (OR: 1.58, 95% CI: 1.29-1.93), being unemployed or retired (OR: 1.55, 95% CI: 1.33-1.81), and living in urban areas (OR: 1.18, 95% CI: 1.09-1.29) were major determinants of anemia. Additionally, we observed a minor but significant positive association between anemia status and CKD, older ages, increased night sleep duration, being a housewife and married, as well as a negative association between anemia and factors including hookah smoking, presence of metabolic syndrome, and overweight and obesity. CONCLUSIONS: Taken together, the anemia prevalence in this study population was of mild public health significance. The major suspected causes might be iron deficiency and chronic disease anemias. Comparably higher rates of anemia were observed amongst women, individuals aged 35-49 years, underweights, unemployed or retired subjects, and urban residents.

Characterization of the first microRNA in human CDH1 that affects cell cycle and apoptosis and indicates breast cancers progression.

The E-cadherin protein (Cadherin 1, gene: CDH1), a master regulator of the human epithelial homeostasis, contributes to the epithelial-mesenchymal transition (EMT) which confers cell migratory features to the cells. The EMT is central to many pathophysiological changes in cancer. Therefore, a better understanding of this regulatory scenario is beneficial for therapeutic regiments. The CDH1 gene is approximately 100 kbp long and consists of 16 exons with a relatively large second intron. Since none microRNA (miRNA) has been identified in CDH1 up to now we screened the CDH1 gene for promising miRNA hairpin structures in silico. Out of the 27 hairpin structures we identified, one stable RNA fold with a promising sequence motive was selected for experimental verification. The exogenous validation of the hairpin sequence was performed by transfection of HEK293T cells and the mature miRNA sequences could be verified by quantitative polymerase chain reaction. The endogenous expression of the mature miRNA provisionally named CDH1-i2-miR-1 could be confirmed in two normal (HEK293T, HUVEK) and five cancer cell lines (MCF7, MDA-MB-231, SW480, HT-29, A549). The functional characterization by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed a suppression of HEK293T cell proliferation. A flow cytometry-based approach showed the ability of CDH1-i2-miR-1 to arrest transfected cells on a G2/M state while annexin staining exemplified an apoptotic effect. BAX and PTEN expression levels were affected following the overexpression with the new miRNA. The in vivo expression level was assessed in 35 breast tumor tissues and their paired nonmalignant marginal part. A fourfold downregulation in the tumor specimens compared to their marginal controls could be observed. It can be concluded that the sequence of the hub gene CDH1 harbors at least one miRNA but eventually even more relevant for the pathophysiology of breast cancer.