Despite the unique properties of clay nanocomposites for cardiovascular applications, there are few data on the hemocompatibility of these nanomaterials. This study represents the first comprehensive investigation of the hemo/biocompatibility of clay nanocomposites in vitro. Nanocomposite coatings of polylactic acid (PLA)-polyethylene glycol (3 wt %)-Cloisite20A nanoclay (3 wt %) were produced using electrospraying technique as potential drug-eluting stent (DES) coatings. Pristine PLA coating served as a control. The coatings ' different structural and biological properties were assessed, including surface morphology, topography, hydrophobicity, mechanics, and the interaction of nanocomposites with blood components, endothelial cells (EC), and bacteria. Findings indicated that all of the coatings were highly hydrophobic with microbead/nanofiber morphology and had antifouling properties. The absorption profiles of plasma proteins were similar for all groups, and nanocomposites did not trigger the coagulation cascade and complement activation. The nanocomposites did not increase hemolysis or platelet and leukocyte adhesion and activation. Interestingly, the nanocomposites exhibited the lowest levels of interleukin-6 production. Cellular experiments showed that the nanocomposites did not reduce ECs survival compared to the control group, and a continuous layer of ECs covered the nanocomposite surfaces after 4 days. These results demonstrate the exceptional hemo/biocompatibility of as-prepared clay nanocomposites as promising biomaterials for implants such as DESs.

Background: Inflammatory bowel disease is a chronic gastrointestinal disorder characterized by relapsing inflammation, disruption of the epithelial barrier, and dysregulated immune responses, leading to substantial morbidity. Conventional in vitro cell cultures and animal models often fail to reproduce the cellular heterogeneity, tissue architecture, and patient-specific features of the disease, limiting mechanistic understanding and therapeutic development. This study aimed to develop and characterize a patient-derived three-dimensional organoid model that closely recapitulates the structural, functional, and molecular hallmarks of the disease. Colonic biopsies from inflamed and non-inflamed regions of patients were embedded in alginate–gelatin scaffolds to generate organoids that maintain physiological tissue architecture and long-term viability. Results: Organoids from non-inflamed tissue maintained uniform spherical morphology with well-defined crypt-like domains, whereas organoids derived from inflamed tissue exhibited irregular architecture, disrupted epithelial junctions, and delayed recovery after passage. Scanning electron microscopy confirmed epithelial discontinuities and surface microfold irregularities in inflamed organoids. Functional viability assessments demonstrated an average survival rate of 71.0% at day 21. Gene expression analysis revealed significant downregulation of the intestinal stem cell marker LGR5 in inflamed organoids compared to controls (0.43 ± 0.05 vs. 1.03 ± 0.06, p = 0.0002), along with marked upregulation of inflammatory chemokines CXCL8 (3.65 ± 0.37, p = 0.0003), CCL2 (2.71 ± 0.17, p = 0.0001), and CXCL10 (4.28 ± 0.15, p < 0.0001). Conclusions: This patient-derived three-dimensional organoid system accurately models disease-associated structural deterioration, impaired regenerative capacity, and inflammatory signaling, providing a physiologically relevant and reproducible platform for mechanistic studies. The model enables high-throughput drug screening, evaluation of patient-specific therapeutic responses, and development of personalized interventions. By bridging the gap between conventional in vitro and in vivo systems, this organoid platform represents a significant advance in tissue engineering and translational gastrointestinal research, facilitating precise investigation of disease pathophysiology and accelerating the development of effective therapies for chronic inflammatory disorders.

Introduction: In infectious diseases, there are essential indices used to describe the disease state. In this study, we estimated the basic reproduction number, R0, peak level, doubling time, and daily growth rate of COVID-19. Methods: This ecological study was conducted in 5 provinces of Iran. The daily numbers of new COVID-19 cases from January 17 to February 8, 2020 were used to determine the basic reproduction number (R0), peak date, doubling time, and daily growth rates in all five provinces. A sensitivity analysis was conducted to estimate epidemiological parameters. Result: The highest and lowest number of deaths were observed in Hamedan (657 deaths) and Chaharmahal and Bakhtiari (54 deaths) provinces, respectively. The doubling time of confirmed cases in Kermanshah and Hamedan ranged widely from 18.59 days (95% confidence interval (CI): 17.38, 20) to 76.66 days (95% CI: 56.36, 119.78). In addition, the highest daily growth rates of confirmed cases were observed in Kermanshah (0.037, 95% CI: 0.034, 0.039) and Sistan and Baluchestan (0.032, 95% CI: 0.030, 0.034) provinces. Conclusion: In light of our findings, it is imperative to tailor containment strategies to the unique epidemiological profiles of each region in order to effectively mitigate the spread and impact of COVID-19. The wide variation in doubling times underscores the importance of flexibility in public health responses. By adapting measures to local conditions, we can better address the evolving dynamics of the pandemic and safeguard the well-being of communities.

Background: Despite substantial efforts to leverage natural killer (NK) cells in cancer immunotherapy, challenges associated with limited cell numbers and sources persist. In this study, our objective is to differentiate NK cells from cord blood hematopoietic stem cells (CB-HSCs) and assess their anti-tumor effects. Methods: Cord blood samples were obtained from pregnant women undergoing normal delivery. Mononuclear cells (MNC) were isolated by gradient centrifugation. Subsequently, HSCs were isolated using the MACs cell separation kit. The isolated HSCs were cultured in NK cell differentiation and expansion media for 21 days and 7 days, respectively. The NK cells were examined for expression of activating markers, cytokine secretion and cytolytic effects by flow cytometry, ELISA and XTT tests, respectively. Results: High-purity HSCs and NK cells were obtained in this study. The CB-HSCs-derived NK cells exhibited significantly higher expression of NKG2D, NKp30, NKp44 and NKp46 receptors (at day 28 of treatment) after treatment by IL-15 and IL-2, compared to the early differentiated NK cells (day 21). NK cells derived from CB-HSCs treated with the combination of IL-15 and IL-2 could robustly lyse breast cancer MCF-7 and K562 cells. Also, the obtained NK cells were able to release higher amounts of TNF-α and IFN-γ cytokines in response to tumor cell experiences. Conclusions: Our findings showed that functionally active CB-HSCs-derived NK cells can be successfully generated ex vivo using a cytokine cocktail without a need for stroma for potential use in the cancer immunotherapy.

NK cells are the first sentinels of the immune system that can recognize and eradicate transformed cells. Their activation without a need for additional signaling have attracted great attention on the use of NK cells as a promising option in cancer immunotherapy. However, the large-scale production of NK cells for successful NK cells therapy is a challenge that needs to be tackled. Engineering NK cells to avoid tumor escape and improve their antitumor potency are the other matters of focus that have widely been studied in the recent years. This paper reviews the most recent advances in the stem cell-derived NK cell technology and discusses the potential of the engineered NK cells for clinical applications in cancer immunotherapy.

Long non-coding RNAs (lncRNAs) play a significant biological role in the regulation of various cellular processes such as cell proliferation, differentiation, apoptosis and migration. In various malignancies, lncRNAs interplay with some main cancer-associated signaling pathways, including the Hippo signaling pathway to regulate the various cellular processes. It has been revealed that the cross-talking between lncRNAs and Hippo signaling pathway involves in gastrointestinal (GI) cancers development and progression. Considering the clinical significance of these lncRNAs, they have also been introduced as potential biomarkers in diagnostic, prognostic and therapeutic strategies in GI cancers. Herein, we review the mechanisms of lncRNA-mediated regulation of Hippo signaling pathway and focus on the corresponding molecular mechanisms and clinical significance of these non-coding RNAs in GI cancers.

Introduction: The relation between physical well-being and chronic pain is complex and involves several subjective and objective covariates. We aimed to assess the role of media-tor, confounder, or interactor played by covariates, including sleep quality, physical activity, perceived stress, smoking, and alcohol drinking in the relation between physical well-being and chronic pain. Method: We used Poisson regression to obtain incidence rate ratios (IRR) of the associa-tion between physical well-being and chronic pain in a cohort study carried out among uni-versity students. We applied General Structural Equation Modeling (GSEM) to assess me-diation, and stratum-specific analysis to distinguish confounding from interaction. We computed Relative Excess Risks due to Interaction (RERI), Attributable Proportion (AP), and Synergy index (S) to measure additive interaction. Results: High physical well-being is related to a large decrease in the risk of chronic pain (IRRTotal Effect= 0.58; 95%CI 0.50-0.81). Perceived stress mediates 12.5% of the total effect of physical well-being on chronic pain. The stratum-specific IRRs of current smokers and non-current smokers were different from each other and were larger than the crude IRR (IRR=1.49; 95% CI: 1.24-1.80), which indicates that smoking could be both confounder and interactor. Interaction analyses showed that physical activity could act as a potential interactor (RERI=0.25; 95% CI: 0.13, 0.60). Conclusion: Perceived stress is an important mediator of the relation between physical well-being and chronic pain, while smoking is both a confounder and an interactor. Our findings may prove useful in distinguishing high-risk from low-risk groups, in the interven-tions aimed at reducing chronic pain.

Introduction: Human endometrial mesenchymal stem cells (hEnMSCs) are a rich source of mesenchymal stem cells (MSCs) with multi-lineage differentiation potential, making them an intriguing tool in regenerative medicine, particularly for the treatment of reproductive and infertility issues. The specific process of germline cell-derived stem cell differentiation remains unknown, the aim is to study novel ways to achieve an effective differentiation method that produces adequate and functioning human gamete cells. Methods: We adjusted the optimum retinoic acid (RA) concentration for enhancement of germ cell-derived hEnSCs generation in 2D cell culture after 7 days in this study. Subsequently, we developed a suitable oocyte-like cell induction media including RA and bone morphogenetic protein 4 (BMP4), and studied their effects on oocyte-like cell differentiation in 2D and 3D cell culture media utilizing cells encapsulated in alginate hydrogel. Results: Our results from microscopy analysis, real-time PCR, and immunofluorescence tests revealed that 10 µM RA concentration was the optimal dose for inducing germ-like cells after 7 days. We examined the alginate hydrogel structural characteristics and integrity by rheology analysis and SEM microscope. We also demonstrated encapsulated cell viability and adhesion in the manufactured hydrogel. We propose that in 3D cell cultures in alginate hydrogel, an induction medium containing 10 µM RA and 50 ng/mL BMP4 can enhance hEnSC differentiation into oocyte-like cells. Conclusion: The production of oocyte-like cells using 3D alginate hydrogel may be viable in vitro approach for replacing gonad tissues and cells.

Background: DNA probes have been widely used as diagnostic tools for translocations. This study sought to design a screening tool using ssDNA probes and chromosome conformation capture (3C) library fragment hybridization. Method: The authors focused on developing a probe for the juxtaposed region of MYC and TRD. Fragments of the MYC gene with a thiol modification (MYC-Au NP probe) were functionalized by gold nanoparticles (Au NPs).Then TRD probes were immobilized on a nitrocellulose surface. Hybridization between DNA probes and 3C library fragments of SKW3 cells was determined by color intensity. Results: Optimal hybridization of the 3C library sample of the cell line to probes showed higher color intensity than human umbilical vein endothelial cells. Conclusion: Combining 3C-based techniques and DNA-DNA hybridization can identify rearrangements in cancer cells.

Introduction: The relation between physical well-being and chronic pain is complex and involves several subjective and objective covariates. We aimed to assess the role of mediator, confounder, or interactor played by covariates, including sleep quality, physical activity, perceived stress, smoking, and alcohol drinking in the relation between physical well-being and chronic pain. Method: We used Poisson regression to obtain incidence rate ratios (IRR) of the association between physical well-being and chronic pain in a cohort study carried out among university students. We applied General Structural Equation Modeling (GSEM) to assess mediation and stratum-specific analyses to distinguish confounding from interaction. We computed Relative Excess Risks due to Interaction (RERI), Attributable Proportion (AP), and the Synergy index (S) to measure additive interaction. Results: High physical well-being is related to a large decrease in the risk of chronic pain (IRRTotal Effect = 0.58; 95% CI: 0.50–0.81). Perceived stress mediates 12.5% of the total effect of physical well-being on chronic pain. The stratum-specific IRRs of current smokers and non-current smokers were different from each other and were larger than the crude IRR (IRR = 1.49; 95% CI: 1.24–1.80), which indicates that smoking could be both confounder and interactor. Interaction analyses showed that physical activity could act as a potential interactor (RERI = 0.25; 95% CI: 0.13, 0.60). Conclusions: Perceived stress is an important mediator of the relation between physical well-being and chronic pain, while smoking is both a confounder and an interactor. Our findings may prove useful in distinguishing high-risk groups from low-risk groups, in the interventions aimed at reducing chronic pain.

Abstract Background Burns are a major cause of death, with infections accounting for 75% of burn-related fatalities. Methicillin-resistant Staphylococcus aureus (MRSA) can infect burn wounds, and conventional antibiotics are not very effective. Mesenchymal stem cells (MSCs) have shown promise in wound healing and protection against infection with alginate scaffold showing synergistic effect and restorative properties.Therefore, we conducted a study comparing the effects of adipose-derived MSCs and bone marrow-derived MSCs, both integrated into alginate scaffolds, in a murine model infected with Staphylococcus aureus. Methods MSCs were isolated and encapsulated in alginate scaffolds. Animal study included seven groups (untreated, treated with antibiotic mupirocin, adipose and bone marrow MSCs, alginate scaffold, adipose and bone marrow MSCs encapsulated in alginate scaffolds). Animals examined for seven days. Histological analyses and bacterial counting were conducted to determine the effectiveness of these methods. Results The treatment reduced the bacterial count and histological analysis of autopsies from the combination therapy group (MSCs with alginate scaffolds) showed significant effect on the wound healing compared to other groups. Conclusion MSCs encapsulated in alginate scaffolds have antimicrobial activity in a model of MRSA-infected burned mice, and accelerates the overall process of burn wound healing.

Introduction: After nearly two years, there is still no proven treatment for infection with severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-the virus that causes Covid-19. Cur-rently, the two most widely known drugs for treating Covid-19 are remdesivir and favipiravir. There-fore, this study aimed to evaluate the effects of remdesivir and favipiravir on Covid-19 clinical out-comes.Methods: A systematic review of the literature on the PubMed and Scopus databases was undertaken to identify studies that have examined the effects of remdesivir and favipiravir on Covid-19 outcomes. To weighted group mean differences for within-and between-group comparisons, odds ratio effect sizes, and random-effects models were used. Subgroup analyses were also con-ducted to determine the effects of potential sources of heterogeneity, which was assessed using the I-squared (I2) test.Results: Twenty-eight studies with a total of 10,871 adult participants were included in the analysis. According to pooled analysis results, there was no statistically significant difference between the remdesivir/favipiravir and control groups in terms of mortality, intensive care unit admissions, or adverse effects (p > 0.05). Mean hospitalization duration was significantly different for those receiving remdesivir (0.1-day increase) and favipiravir (0.06-day decrease), but these findings included significant levels of publication bias. Treatment duration was found to be a significant source of heterogeneity in the mortality results.Conclusion: Remdesivir and favipi-ravir have no effect on mortality, intensive care unit admissions, or duration of hospitalization for Covid-19 patients.

Background: Chronic pain and depression represent two global health problems with considerable economic conse-quences. Although existing literature reports on the relation between depression and pain conditions, meta-analytic evidence backing the mediating role of sleep disturbance as one of the main symptoms of depression is scarce. To examine the extent to which sleep disturbance mediates the depression-chronic pain association, we conducted a systematic review and meta-analysis of the associations of chronic pain, depression, and sleep quality.Methods: We systematically searched for literature in MEDLINE and other relevant databases and identified cohort and case-co ntrol studies on depression, sleep disturbance, and chronic pain. Forty-nine studies were eligible, with a total population of 120 489 individuals. We obtained direct and indirect path coefficients via two-stage meta-ana-lytic structural equation modelling, examined heterogeneity via subgroup analyses, and evaluated primary studies quality.Results: We found a significant, partial mediation effect of sleep disturbance on the relation between depression and chronic pain. The pooled path coefficient (coef.) of the indirect effect was 0.03 (95% confidence interval [CI]: 0.01-0.05) and accounted for 12.5% of the total effect of depression on chronic pain. This indirect effect also existed for cohort studies (coef. 0.02; 95% CI: 0.002-0.04), European studies (coef. 0.03; 95% CI: 0.004-0.05), and studies that adjusted for confounders (coef. 0.04; 95% CI: 0.01-0.09).Conclusions: Sleep disturbance partially mediates the association between depression and pain. Although plausible mechanisms could explain this mediation effect, other explanations, including reverse causation, must be further explored.Systematic review protocol: PROSPERO CRD42022338201.

Burns injuries are prone to hospital-acquired infections, and Pseudomonas aeruginosa is one of the most common causes of mortality and morbidity in patients with burn injuries. Thus, this study aimed to analyze the effects of topical treatment with bone marrow (BM-MSC) and adipose mesenchymal stem cells (AD-MSC) encapsulated in collagen and fibrin scaffolds in a Balb/c model of burn wound infection. Extraction of stem cells from adipose and bone marrow tissue of rats was performed and cells were characterized using standard methods. Then, collagen, fibrin and collagen-fibrin scaffolds were constructed and the extracted cells were encapsulated in all three scaffolds. Then, 3rd degree burn was induced in mice and 1.5 × 108 (CFU/ml) of P. aeruginosa was introduced to the burn wound. Subsequently, after 24 h of inducing wound infection, encapsulated MSCs were introduced as dressings to burn wound infection and microbial load as well as rate of wound infection healing was measured. The results of this study showed that the use of BM-MSC and AD-MSC encapsulated in collagen-fibrin scaffold reduced the bacteria load down to 54 and 21 CFU/gr, respectively (P < 0.05). Moreover, BM-MSC and AD-MSC encapsulated in collagen-fibrin showed 80% and 75% wound healing, respectively (P < 0.05). Also, we found no significant between cell origin and healing. Encapsulation of MSCs into collagen-fibrin scaffolds could be effective not only against P. aeruginosa infection, but also healing and regeneration of burn wound.

Background and aim Adipocytokines play an important role in obstructive sleep apnea (OSA) by mediating inflammatory responses. Previous studies have reported that OSA is related to a change in the serum levels of adipocytokines; however, the results are still controversial. This meta-analysis aimed to assess the relationship between OSA and circulating level of adipocytokines in adults and children. Methods A comprehensive search was conducted in databases of Medline/PubMed and Scopus for pertinent articles published since their inception to July 2022. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to assess the strength of the relationship between the concentrations of adipocytokines with OSA. Results In the overall analysis, contrary to IL-10, which showed a significant reduction, IL-1β, IL-4, IL-8, IL-17, and IFN- gamma showed higher levels in OSA patients in comparison with control groups (p <0.05). For adults, IL-1β, IL-8, IL-17, IL-18, vaspin, visfatin, and chemerin were linked to a greater serum levels in patients with OSA, while, IL-5 and IL-10 were detected significantly lower in adults with OSA in comparison with healthy adults (p <0.05). In children with OSA, the serum levels of IL-4, IL-8, IL-12, IL-17, IL-23, and IFN-gamma were significantly higher than healthy children (p <0.05). Conclusion The levels of inflammatory markers were found to be higher in OSA patients compared with control individuals, suggesting that adipocytokines may contribute to the pathology of OSA.

Precise engineering of surface properties is essential for improving bio/hemocompatibility of medical implants. In this study, potential of electrospraying (ES) as a coating method to control surface properties was evaluated in vitro. Poly (lactic acid) was coated on 316 L stainless steel plates by ES and spin-coating methods. Surface topography and morphology were studied using confocal and scanning electron microscope (SEM), respectively. Surface hydrophobicity and mechanical properties were investigated by contact angle and nanoindentation tests. Hemocompatibility of samples evaluated using protein adsorption, hemolysis, blood coagulation, complement system and leukocyte activation experiments. Platelet response to the coatings was examined using LDH assay, SEM and ELISA tests. Cell viability studies performed on human endothelial cells using MTT assay and SEM after 1, 4 and 7 days. SEM was used to consider formation of pseudomonas aeruginosa biofilms on the coatings. The results showed that ES increased hydrophobicity (122֯ vs 90֯) and surface roughness (2 μm vs 1.2 μm) but reduced surface stiffness (200 MPa vs 10800 MPa) in comparison to spin-coated samples. ES-coatings had microbead/nanofiber morphology while spin-coated samples had micro/nanoporous structure. Importantly, an almost confluent layer of endothelial cells was observed on ES-coated samples after 4 days in contrast to spin-coated ones. Various blood experiments revealed both coatings were hemocompatible and there was no significant difference among ES and spin-coated samples. Furthermore, ES-coated samples showed significantly lower propensity for biofilm formation. In conclusion, in vitro results revealed potential of ES to engineer different coating properties including hemo/biocompatibility and biofilm resistance for cardiovascular implants applications.

Abstract Background: PRF as one of the favorable scaffolds in Regenerative Endodontic Treatment (RET), has several limitations such as the need for blood sampling and special equipment. High available commercial scaffolds such as fibrin are able to meet all the necessary requirements of dentin tissue engineering. The present study was designed to evaluate the effect of PRF and fibrin gel, with and without the presence of EDTA-treated radicular dentin segments on SCAP viability, proliferation, migration, and differentiation.Methods: Radicular dentin were prepared from extracted teeth and treated by EDTA 17% .The samples were divided into 6 groups: Dentin/PRF/Cell, Dentin/Fibrin/Cell, Dentin/Cell, PRF/Cell, Fibrin/Cell and Cell (Control). SCAP viability was assessed using MTT assay. Gene expression levels of odontogenic markers [Dentin sialophosphoprotein (DSPP), Dentin matrix protein 1(DMP1), Collagen type I Alpha 1(COL 1A1) and Alkaline phosphatase (ALP) were assessed using qrt-PCR. Cell migration were also evaluated by means of scratch test. Results: The results of MTT assay at showed that the viability of SCAP significantly increased after 7 days for both groups containing fibrin (P <0.05). The viability of SCAP seeded on Dentin/PRF and PRF significantly decreased after 7 days (P <0.001). The odontogenic markers were significantly expressed for both scaffolds in the presence of dentin segment (p<0.05). Significant decrease in scratch area was seen in Fibrin/Dentin group (p < 0.001)Conclusions:Fibrin beside EDTA-treated dentin showed great ability in survival, proliferation, differentiation, and migration of SCAP rather than PRF.

Introduction: Chronic pain represents a global health problem with a considerable economic burden. The relation of alcohol intake and chronic pain conditions was assessed in several studies with conflicting results. We used doseeresponse meta-analysis techniques to answer the question of whether alcohol intake is related to chronic pain occurrence. Methods: We searched MEDLINE, Embase, and other databases to identify cohort and case-control studies on alcohol consumption and chronic pain. Sixteen studies were eligible with a total population of 642 587 individuals. Fixed-effects and random-effects pooled estimates were obtained by weighting log odds ratios (ORs) in case-control studies and log incidence rate ratios in cohort studies by the inverse of their variance. A heterogeneity assessment and a doseeresponse analysis were carried out. Quality scoring was also performed. Results: Our results show that any alcohol consumption was related to lower odds of chronic pain (pooled OR 1/4 0.76; 95% confidence interval [CI], 0.61e0.95). The association was non-linear. The ORs by quartile of alcohol doses were as follows: OR2nd quartile 1/4 0.74; 95% CI, 0.64e0.87; OR3rd quartile 1/4 0.67; 95% CI, 0.53e0.86; and OR4th quartile 1/4 0.75; 95% CI, 0.50e1.14. This association was observed for cohort studies (OR 1/4 0.77; 95% CI, 0.61e0.98) and European studies (OR 1/4 0.65; 95% CI, 0.48e0.87) only. Studies with complete adjustment for confounding factors showed a stronger relation than those with incomplete adjustment (OR 1/40.69; 95% CI, 0.48e0.99 and OR 1/40.85; 95% CI, 0.65e1.11, respectively). Conclusion: Alcohol consumption presents a non-linear inverse association with the occurrence of chronic pain. Although plausible mechanisms could explain this protective effect, other explanations, including reverse causation, are probable.