Porphyromonas gingivalis GroEL exacerbates orthotopic allograft transplantation vasculopathy via impairment of endothelial cell function.

Orthotopic allograft transplantation (OAT) is a significant approach to addressing organ failure. However, persistent immune responses to the allograft affect chronic rejection, which induces OAT vasculopathy (OATV) and organ failure. Porphyromonas gingivalis can infiltrate remote organs via the bloodstream, thereby intensifying the severity of cardiovascular, respiratory, and neurodegenerative diseases and cancer. GroEL, a virulence factor of P. gingivalis promotes pro-inflammatory cytokine production in host cells, which assumes to play a pivotal role in the pathogenesis of cardiovascular diseases. Although the aggravation of OATV is attributable to numerous factors, the role of GroEL remains ambiguous. Therefore, this study aimed to investigate the impact of GroEL on OATV. Aortic grafts extracted from PVG/Seac rats were transplanted into ACI/NKyo rats and in vitro human endothelial progenitor cell (EPC) and coronary artery endothelial cell (HCAEC) models. The experimental findings revealed that GroEL exacerbates OATV in ACI/NKyo rats by affecting EPC and smooth muscle progenitor cell (SMPC) function and enabling the anomalous accumulation of collagen. In vitro, GroEL spurs endothelial-mesenchymal transition in EPCs, reduces HCAEC tube formation and barrier function by downregulating junction proteins, accelerates HCAEC aging by lowering mitochondrial membrane potential and respiratory function, and impedes HCAEC migration by modulating cytoskeleton-associated molecules. This study suggests that P. gingivalis GroEL could potentially augment OATV by impacting vascular progenitor and endothelial cell functions.

GroEL of Porphyromonas gingivalis-induced microRNAs accelerate tumor neovascularization by downregulating thrombomodulin expression in endothelial progenitor cells.

We found that GroEL in Porphyromonas gingivalis accelerated tumor growth and increased mortality in tumor-bearing mice; GroEL promoted proangiogenic function, which may be the reason for promoting tumor growth. To understand the regulatory mechanisms by which GroEL increases the proangiogenic function of endothelial progenitor cells (EPCs), we explored in this study. In EPCs, MTT assay, wound-healing assay, and tube formation assay were performed to analyze its activity. Western blot and immunoprecipitation were used to study the protein expression along with next-generation sequencing for miRNA expression. Finally, a murine tumorigenesis animal model was used to confirm the results of in vitro. The results indicated that thrombomodulin (TM) direct interacts with PI3 K/Akt to inhibit the activation of signaling pathways. When the expression of TM is decreased by GroEL stimulation, molecules in the PI3 K/Akt signaling axis are released and activated, resulting in increased migration and tube formation of EPCs. In addition, GroEL inhibits TM mRNA expression by activating miR-1248, miR-1291, and miR-5701. Losing the functions of miR-1248, miR-1291, and miR-5701 can effectively alleviate the GroEL-induced decrease in TM protein levels and inhibit the proangiogenic abilities of EPCs. These results were also confirmed in animal experiments. In conclusion, the intracellular domain of the TM of EPCs plays a negative regulatory role in the proangiogenic capabilities of EPCs, mainly through direct interaction between TM and PI3 K/Akt to inhibit the activation of signaling pathways. The effects of GroEL on tumor growth can be reduced by inhibiting the proangiogenic properties of EPCs through the inhibition of the expression of specific miRNAs.

Identification of Genetic Variants Associated with Severe Myocardial Bridging through Whole-Exome Sequencing.

Myocardial bridging (MB) is a congenital coronary artery anomaly and an important cause of angina. The genetic basis of MB is currently unknown. This study used a whole-exome sequencing technique and analyzed genotypic differences. Eight coronary angiography-confirmed cases of severe MB and eight age- and sex-matched control patients were investigated. In total, 139 rare variants that are potentially pathogenic for severe MB were identified in 132 genes. Genes with multiple rare variants or co-predicted by ClinVar and CADD/REVEL for severe MB were collected, from which heart-specific genes were selected under the guidance of tissue expression levels. Functional annotation indicated significant genetic associations with abnormal skeletal muscle mass, cardiomyopathies, and transmembrane ion channels. Candidate genes were reviewed regarding the functions and locations of each individual gene product. Among the gene candidates for severe MB, rare variants in DMD, SGCA, and TTN were determined to be the most crucial. The results suggest that altered anchoring proteins on the cell membrane and intracellular sarcomere unit of cardiomyocytes play a role in the development of the missed trajectory of coronary vessels. Additional studies are required to support the diagnostic application of cardiac sarcoglycan and dystroglycan complexes in patients with severe MB.

Exploring the Potential Performance of Fibroscan for Predicting and Evaluating Metabolic Syndrome using a Feature Selected Strategy of Machine Learning.

Metabolic syndrome (MetS) includes several conditions that can increase an individual's predisposition to high-risk cardiovascular events, morbidity, and mortality. Non-alcoholic fatty liver disease (NAFLD) is a predominant cause of cirrhosis, which is a global indicator of liver transplantation and is considered the hepatic manifestation of MetS. FibroScan® provides an accurate and non-invasive method for assessing liver steatosis and fibrosis in patients with NAFLD, via a controlled attenuation parameter (CAP) and liver stiffness measurement (LSM or E) scores and has been widely used in current clinical practice. Several machine learning (ML) models with a recursive feature elimination (RFE) algorithm were applied to evaluate the importance of the CAP score. Analysis by ANOVA revealed that five symptoms at different CAP and E score levels were significant. All eight ML models had accuracy scores > 0.9, while treebags and random forest had the best kappa values (0.6439 and 0.6533, respectively). The CAP score was the most important variable in the seven ML models. Machine learning models with RFE demonstrated that using the CAP score to identify patients with MetS may be feasible. Thus, a combination of CAP scores and other significant biomarkers could be used for early detection in predicting MetS.

Animal Models for Heart Transplantation Focusing on the Pathological Conditions.

Cardiac transplant recipients face many complications due to transplant rejection. Scientists must conduct animal experiments to study disease onset mechanisms and develop countermeasures. Therefore, many animal models have been developed for research topics including immunopathology of graft rejection, immunosuppressive therapies, anastomotic techniques, and graft preservation techniques. Small experimental animals include rodents, rabbits, and guinea pigs. They have a high metabolic rate, high reproductive rate, small size for easy handling, and low cost. Additionally, they have genetically modified strains for pathological mechanisms research; however, there is a lacuna, as these research results rarely translate directly to clinical applications. Large animals, including canines, pigs, and non-human primates, have anatomical structures and physiological states that are similar to those of humans; therefore, they are often used to validate the results obtained from small animal studies and directly speculate on the feasibility of applying these results in clinical practice. Before 2023, PubMed Central® at the United States National Institute of Health's National Library of Medicine was used for literature searches on the animal models for heart transplantation focusing on the pathological conditions. Unpublished reports and abstracts from conferences were excluded from this review article. We discussed the applications of small- and large-animal models in heart transplantation-related studies. This review article aimed to provide researchers with a complete understanding of animal models for heart transplantation by focusing on the pathological conditions created by each model.

Tumor Necrosis Factor Superfamily 14 (LIGHT) Restricts Neovascularization by Decreasing Circulating Endothelial Progenitor Cells and Function.

Tumor necrosis factor superfamily 14 (TNFSF14) is also known as the LT-related inducible ligand (LIGHT). It can bind to the herpesvirus invasion mediator and lymphotoxin-ß receptor to perform its biological activity. LIGHT has multiple physiological functions, including strengthening the synthesis of nitric oxide, reactive oxygen species, and cytokines. LIGHT also stimulates angiogenesis in tumors and induces the synthesis of high endothelial venules; degrades the extracellular matrix in thoracic aortic dissection, and induces the expression of interleukin-8, cyclooxygenase-2, and cell adhesion molecules in endothelial cells. While LIGHT induces tissue inflammation, its effects on angiogenesis after tissue ischemia are unclear. Thus, we analyzed these effects in the current study. In this study, the animal model of hind limb ischemia surgery in C57BL/6 mice was performed. Doppler ultrasound, immunohistochemical staining, and Western blotting were employed to analyze the situation of angiogenesis. In addition, human endothelial progenitor cells (EPCs) were used for in vitro studies to analyze the possible mechanisms. The results in the animal study showed that LIGHT injection inhibited angiogenesis in ischemic limbs. For the in vitro studies, LIGHT inhibited the expression of integrins and E-selectin; decreased migration and tube formation capabilities, mitochondrial respiration, and succinate dehydrogenase activity; and promoted senescence in EPCs. Western blotting revealed that the impairment of EPC function by LIGHT may be due to its effects on the proper functioning of the intracellular Akt signaling pathway, endothelial nitrite oxide synthase (eNOS), and mitochondrial respiration. In conclusion, LIGHT inhibits angiogenesis after tissue ischemia. This may be related to the clamped EPC function.

Prediction of the Duration to Next Admission for an Acute Affective Episode in Patients with Bipolar I Disorder.

Objective: Predicting disease relapse and early intervention could reduce symptom severity. We attempted to identify potential indicators that predict the duration to next admission for an acute affective episode in patients with bipolar I disorder. Methods: We mathematically defined the duration to next psychiatric admission and performed single-variate regressions using historical data of 101 patients with bipolar I disorder to screen for potential variables for further multivariate regressions. Results: Age of onset, total psychiatric admissions, length of lithium use, and carbamazepine use during the psychiatric hospitalization contributed to the next psychiatric admission duration positively. The all-in-one found that hyperlipidemia during the psychiatric hospitalization demonstrated a negative contribution to the duration to next psychiatric admission; the last duration to psychiatric admission, lithium and carbamazepine uses during the psychiatric hospitalization, and heart rate on the discharge day positively contributed to the duration to next admission. Conclusion: We identified essential variables that may predict the duration of bipolar I patients' next psychiatric admission. The correlation of a faster heartbeat and a normal lipid profile in delaying the next onset highlights the importance of managing these parameters when treating bipolar I disorder.

Transcriptomic Profiling Unravels Novel Deregulated Gene Signatures Associated with Acute Myocardial Infarction: A Bioinformatics Approach.

Acute myocardial infarction (AMI) is a severe disease with elevated morbidity and mortality rate worldwide. This is attributed to great losses of cardiomyocytes, which can trigger the alteration of gene expression patterns. Although several attempts have been made to assess the AMI biomarkers, to date their role in rescuing myocardial injury remains unclear. Therefore, the current study investigated three independent microarray-based gene expression datasets from AMI patients (n = 85) and their age-sex-matched healthy controls (n = 70), to identify novel gene signatures that might be involved in cardioprotection. The differentially expressed genes (DEGs) were analyzed using 'GEO2R', and weighted gene correlation network analysis (WGCNA) was performed to identify biomarkers/modules. We found 91 DEGs, of which the number of upregulated and downregulated genes were 22 and 5, respectively. Specifically, we found that the deregulated genes such as ADOR-A3, BMP6, VPS8, and GPx3, may be associated with AMI. WGCNA revealed four highly preserved modules among all datasets. The 'Enrichr' unveiled the presence of miR-660 and STAT1, which is known to affect AMI severity. Conclusively, these genes and miRNA might play a crucial role the rescue of cardiomyocytes from severe damage, which could be helpful in developing appropriate therapeutic strategies for the management of AMI.

Identification of Patients with Potential Atrial Fibrillation during Sinus Rhythm Using Isolated P Wave Characteristics from 12-Lead ECGs.

Atrial fibrillation (AF) is largely underdiagnosed. Previous studies using deep neural networks with large datasets have shown that screening AF with a 12-lead electrocardiogram (ECG) during sinus rhythm (SR) is possible. However, the poor availability of these trained models and the small size of the retrievable datasets limit its reproducibility. This study proposes an approach to generate explainable features for detecting AF during SR with limited data. We collected 94,224 12-lead ECGs from 64,196 patients from Taipei Medical University Hospital. We selected ECGs during SR from 213 patients before AF diagnosis and randomly selected 247 age-matched participants without AF records as the controls. We developed a signal-processing technique, MA-UPEMD, to isolate P waves, and quantified the spatial and temporal features using principal component analysis and inter-lead relationships. By combining these features, the machine learning models yielded AUC of 0.64. We showed that, even with this limited dataset, the P wave, representing atrial electrical activity, is depicted by our proposed approach. The extracted features performed better than the bandpass filter-extracted P waves and deep neural network model. We provided a physiologically explainable and reproducible approach for classifying patients with AF during SR.

Luminal pressure gradient and risk of arteriovenous fistula nonmaturation.

While arteriovenous fistula (AVF) nonmaturation is a major issue of hemodialysis care, an effective treatment to improve AVF maturation remains lacking. AVF introduces pulsatile arterial blood flow into its venous limb and produces high luminal pressure gradient, which may have adverse effect on vascular remodeling. As such, the aim of the present study is to investigate effect of luminal pressure gradient on AVF nonmaturation. This single-center, prospective observational study includes patients receiving autologous AVF creation. Participants received early postoperative ultrasound 5-7 days after surgery to collect parameters including diameters, flow rates, and volume at inflow and outflow sites. Luminal pressure gradient was estimated by using modified Bernoulli equation. The outcome was spontaneous AVF maturation within 8 weeks after surgery without intervention. Thirty patients were included, of which the mean age was 66.9 years and 70% were male. At the end of study, 13 (43.3%) patients had spontaneous AVF maturation. All demographic and laboratory characteristics were similar between patients with mature and nonmature AVF. Regarding ultrasonographic parameters, nonmature AVF showed significantly higher inflow/outflow diameter ratio, inflow velocity, and luminal pressure gradient. While these 3 parameters were significantly correlated, multivariate logistic regression showed their significant association with AVF nonmaturation. Receiver operating characteristic curve exhibited their high predictive value for AVF nonmaturation. Our findings showed that higher inflow/outflow ratio, inflow velocity, and AVF luminal pressure gradient in early postoperative ultrasound predicted risk of AVF nonmaturation. Reducing inflow/outflow diameter ratio or inflow rate may be an approach to improve AVF maturation. The predictive value of this early assessment might have impact on the clinical practice of AVF care.

Annoying Psoriasis and Atopic Dermatitis: A Narrative Review.

Skin is an important organ that mainly functions as a barrier. Skin diseases can damage a person's self-confidence and reduce their willingness to socialize, as well as their social behavior and willingness. When the skin appearance is abnormal, in addition to affecting the quality of life, it often leads to personal, social, and psychological dysfunction and even induces depression. Psoriasis and atopic dermatitis are common chronic skin diseases. Their prevalence in the world is 3-10%, and there is an increasing trend year by year. These congenital or acquired factors cause the dysfunction of the immune system and then destroy the barrier function of the skin. Because these patients are flooded with a variety of inflammatory mediators, this causes skin cells to be in chronic inflammation. Therefore, psoriasis and atopic dermatitis are also considered systemic chronic inflammatory diseases. In the healthcare systems of developed countries, it is unavoidable to spend high costs to relieve symptoms of psoriasis and atopic dermatitis patients, because psoriasis and atopic dermatitis have a great influence on individuals and society. Giving a lot of attention and developing effective treatment methods are the topics that the medical community must work on together. Therefore, we used a narrative review manuscript to discuss pathogenesis, clinical classification, incidence, and treatment options, including topical medication, systemic therapeutics, immunosuppressive medication for psoriasis, and atopic dermatitis, as well as also comparing the differences between these two diseases. We look forward to providing readers with comprehensive information on psoriasis and atopic dermatitis through this review article.

Far-Infrared Therapy Decreases Orthotopic Allograft Transplantation Vasculopathy.

Orthotopic allograft transplantation (OAT) is a major strategy for solid heart and kidney failure. However, the recipient's immunity-induced chronic rejection induces OAT vasculopathy that results in donor organ failure. With the exception of immunosuppressive agents, there are currently no specific means to inhibit the occurrence of OAT vasculopathy. On the other hand, far-infrared (FIR) therapy uses low-power electromagnetic waves given by FIR, with a wavelength of 3-25 µm, to improve human physiological functions. Previous studies have shown that FIR therapy can effectively inhibit inflammation. It has also been widely used in adjuvant therapy for various clinical diseases, especially cardiovascular diseases, in recent years. Thus, we used this study to explore the feasibility of FIR in preventing OAT vasculopathy. In this study, the model of transplantation of an aorta graft from PVG/Seac rat to ACI/NKyo rat, and in vitro model of human endothelial progenitor cells (EPCs) was used. In this report, we presented that FIR therapy decreased the serious of vasculopathy in OAT-recipient ACI/NKyo rats via inhibiting proliferation of smooth muscle cells, accumulation of collagen, and infiltration of fibroblast in the vessel wall; humoral and cell-mediated immune responses were decreased in the spleen. The production of inflammatory proteins/cytokines also decreased in the plasma. Additionally, FIR therapy presented higher mobilization and circulating EPC levels associated with vessel repair in OAT-recipient ACI/NKyo rats. In vitro studies demonstrated that the underlying mechanisms of FIR therapy inhibiting OAT vasculopathy may be associated with the inhibition of the Smad2-Slug axis endothelial mesenchymal transition (EndoMT). Thus, FIR therapy may be the strategy to prevent chronic rejection-induced vasculopathy.

Health belief model in predicting treatment intention among healthy and gynecologic cancer women with sexual dysfunction: Structural equation modeling.

OBJECTIVE: Few large-scale studies have focused on the effect of gynecologic cancer compared with other biopsychosocial factors on willingness to seek treatment among women with sexual dysfunction. The aim of study was to identify predictors of the intention to treat female sexual dysfunction (FSD) among sociodemographic factors, physiologic factors, psychologic factors, gynecologic cancer, and health belief model (HBM). MATERIALS AND METHODS: This study was a cross-sectional, hospital-based survey conducted from October 2013 to September 2019. Participants included healthy women and gynecologic cancer survivors who were aged 20 years or older and had been in a monogamous relationship for at least 12 months. They were enrolled in the gynecologic departments in southern Taiwan. Those who met DSM-5 criteria of sexual dysfunction were analyzed with Structural equation modeling. Intention to seek treatment was the primary outcome. RESULTS: 448 of 643 women met DSM-5 sexual dysfunction. The mean age was 42.0 years (range: 21.8-68.1 years). Fifty-eight percent of women reported sexual treatment intention. The model fit was good: χ2 = 367.42, P < .001, χ2/df = 2.83, CFI = 0.933, TLI = 0.921, and RMSEA = 0.066 (95%CI: 0.058-0.074). Perceived severity, perceived benefits, perceived barriers, cue to action, self-efficacy and university education at least significantly predicted treatment intention. There were no significant differences in treatment intention regarding age and gynecologic cancer. Self-efficacy was the strongest predictor, which directly affected treatment intention (P = .001). Perceived severity was the second strongest predictor, mainly affecting treatment intention indirectly (P = .01). Perceived barriers was the third strongest predictor (P = .001), indirectly and negatively affected treatment intention. CONCLUSIONS: Five out of six HBM factors and university education at least could significantly predict the intention to treat FSD. Gynecologic cancer was not a significant predictor.

Identification of a Novel Theranostic Signature of Metabolic and Immune-Inflammatory Dysregulation in Myocardial Infarction, and the Potential Therapeutic Properties of Ovatodiolide, a Diterpenoid Derivative.

Myocardial infarction (MI) is a multifactorial global disease, recognized as one of the leading causes of cardiovascular morbidity and mortality. Timely and correct diagnoses and effective treatments could significantly reduce incidence of complications and improve patient prognoses. In this study, seven unconventional differentially expressed genes (DEGs) (MAN2A2, TNFRSF12A, SPP1, CSNK1D, PLAUR, PFKFB3, and CXCL16, collectively termed the MTSCPPC signature) were identified through integrating DEGs from six MI microarray datasets. The pathological and theranostic roles of the MTSCPPC signature in MI were subsequently analyzed. We evaluated interactions of the MTSCPPC signature with ovatodiolide, a bioactive compound isolated from Anisomeles indica (L.) Kuntze, using in silico molecular docking tools and compared it to specific inhibitors of the members of the MTSCPPC signature. Single-cell transcriptomic analysis of the public databases revealed high expression levels of the MTSCPPC signature in immune cells of adult human hearts during an MI event. The MTSCPPC signature was significantly associated with the cytokine-cytokine receptor interactions, chemokine signaling, immune and inflammatory responses, and metabolic dysregulation in MI. Analysis of a micro (mi)RNA regulatory network of the MTSCPPC signature suggested post-transcriptional activation and the roles of miRNAs in the pathology of MI. Our molecular docking analysis suggested a higher potential for ovatodiolide to target MAN2A2, CSNK1D, and TNFRSF12A. Collectively, the results derived from the present study further advance our understanding of the complex regulatory mechanisms of MI and provide a potential MI theranostic signature with ovatodiolide as a therapeutic candidate.

Inhibition of ß-catenin signaling attenuates arteriovenous fistula thickening in mice by suppressing myofibroblasts.

BACKGROUND: Arteriovenous fistula (AVF) is the most important vascular access for hemodialysis; however, preventive treatment to maintain the patency of AVFs has not been developed. In endothelium, ß-catenin functions in both the intercellular adherens complex and signaling pathways that induce the transition of endothelial cells to myofibroblasts in response to mechanical stimuli. We hypothesize that mechanical disturbances in the AVF activate ß-catenin signaling leading to the transition of endothelial cells to myofibroblasts, which cause AVF thickening. The present study aimed to test this hypothesis. METHODS: Chronic kidney disease in mice was induced by a 0.2% adenine diet. AVFs were created by aortocaval puncture. Human umbilical vein endothelial cells (HUVECs) were used in the cell experiments. A pressure-culture system was used to simulate mechanical disturbances of the AVF. RESULTS: Co-expression of CD31 and smooth muscle alpha-actin (αSMA), loss of cell-cell adhesions, and the expression of the myofibroblast marker, integrin subunit ß6 (ITGB6), indicated transition to myofibroblasts in mouse AVF. Nuclear translocation of ß-catenin, decreased axin2, and increased c-myc expression were also observed in the AVF, indicating activated ß-catenin signaling. To confirm that ß-catenin signaling contributes to AVF lesions, ß-catenin signaling was inhibited with pyrvinium pamoate; ß-catenin inhibition significantly attenuated AVF thickening and decreased myofibroblasts. In HUVECs, barometric pressure-induced nuclear localization of ß-catenin and increased expression of the myofibroblast markers, αSMA and ITGB6. These changes were attenuated via pretreatment with ß-catenin inhibition. CONCLUSIONS: The results of this study indicate that mechanical disturbance in AVF activates ß-catenin signaling to induce the transition of endothelial cells to myofibroblasts. This signaling cascade can be targeted to maintain AVF patency.

Evaluation of sexual dysfunction in gynecologic cancer survivors using DSM-5 diagnostic criteria.

BACKGROUND: In gynecologic cancer survivors, female sexual dysfunction (FSD) remains under-investigated. We attempted to estimate the prevalence of FSD associated with distress in gynecologic cancer survivors using diagnostic and statistical manual of mental disorders fifth edition (DSM-5) diagnostic criteria and to identify women at risk for FSD. METHODS: We conducted a cross-sectional analysis of premenopausal women aged 20-50 with various gynecologic cancers at least one year after treatment between January 2017 and December 2019. Data of sociodemographics and physical conditions were collected via face-to-face interview during outpatient clinic visits. The domains we used to define FSD were based on DSM-5 diagnostic criteria. Statistical analysis was carried out using Student's t test, Chi-square test and multiple logistic regression. RESULTS: A total of 126 gynecologic cancer survivors with a mean age of 42.4 years were included for analysis and 55 of them (43.7%) were diagnosed as having FSD associated with distress based on DSM-5 criteria. More than half of women (65.1%) reported decreased sexual satisfaction after cancer treatment. According to DSM-5 definition, the most common female sexual disorders were sexual interest/arousal disorder (70.9%), followed by genitopelvic pain/penetration disorder (60.0%), and orgasmic disorder (20.0%). In multiple logistic regression model, endometrial cancer diagnosis was the only independent factor predicting less influence of cancer treatment on FSD (OR 0.370; 95% CI 0.160, 0.856). CONCLUSION: The first study to use DSM-5 criteria for estimation of FSD prevalence. This enables clinicians to identify which women are actually needed to seek medical help. A prevalence of 43.7% of FSD associated with distress was found in a group of gynecologic cancer survivors with the most common being sexual interest/arousal disorder. Endometrial cancer survivors were at low risk for developing FSD after treatment.

The Impact of SARS-CoV-2 Infection, and Application of Immunosuppressive Agents in Kidney Transplant Recipients Suffering from COVID-19.

In December 2019, the COVID-19 pandemic began to ravage the world quickly, causing unprecedented losses in human life and the economy. A statistical study revealed that the proportion of solid organ transplant (SOT) recipients with severe symptoms and deaths after being infected by SARS-CoV-2 is considerably higher than that of non-SOT recipients, and the prognosis is relatively poor. In addition, the clinical manifestation of SOT recipients suffering from COVID-19 is different from that of general COVID-19 patients. Acute kidney injury (AKI) is a common complication in COVID-19 patients, and it is likely more common among SOT recipients infected with SARS-CoV-2. Clinical experts consider that SOT recipients have long-term treatment with immunosuppressants, and the comorbidities are driven by a high rate of severe symptoms and mortality. Orthotopic kidney allograft transplantation is an effective treatment for patients suffering from end-stage kidney disease/kidney failure through which they can easily extend their life. Indeed, kidney transplant recipients have suffered significant damage during this pandemic. To effectively reduce the severity of symptoms and mortality of kidney transplant recipients suffering from COVID-19, precise application of various drugs, particularly immunosuppressants, is necessary. Therefore, herein, we will collate the current clinical experience of treating COVID-19 infection in kidney transplant recipients and discuss the adjustment of patients using immunosuppressive agents in the face of COVID-19.

Tissue-Engineered Vascular Graft with Co-Culture of Smooth Muscle Cells and Human Endothelial Vein Cells on an Electrospun Poly(lactic-co-glycolic acid) Microtube Array Membrane.

Coronary artery disease is one of the major diseases that plagues today's modern society. Conventional treatments utilize synthetic vascular grafts such as Dacron® and Teflon® in bypass graft surgery. Despite the wide adaptation, these synthetic grafts are often plagued with weaknesses such as low hemocompatibility, thrombosis, intimal hyperplasia, and risks of graft infection. More importantly, these synthetic grafts are not available at diameters of less than 6 mm. In view of these challenges, we strived to develop and adapt the electrospun Poly Lactic-co-Glycolic Acid (PLGA) Microtube Array Membrane (MTAM) vascular graft for applications smaller than 6 mm in diameter. Homogenously porous PLGA MTAMs were successfully electrospun at 5.5-8.5 kV under ambient conditions. Mechanically, the PLGA MTAMs registered a maximum tensile strength of 5.57 ± 0.85 MPa and Young's modulus value of 1.134 ± 0.01 MPa; while MTT assay revealed that seven-day Smooth Muscle Cells (SMCs) and Human Umbilical Vein Endothelial Cells (HUVECs) registered a 6 times and 2.4 times higher cell viability when cultured in a co-culture setting in medium containing α-1 haptaglobulin. When rolled into a vascular graft, the PLGA MTAMs registered an overall degradation of 82% after 60 days of cell co-culture. After eight weeks of culturing, immunohistochemistry staining revealed the formation of a monolayer of HUVECs with tight junctions on the surface of the PLGA MTAM, and as for the SMCs housed within the lumens of the PLGA MTAMs, a monolayer with high degree of orientation was observed. The PLGA MTAM registered a burst pressure of 1092.2 ± 175.3 mmHg, which was sufficient for applications such as small diameter blood vessels. Potentially, the PLGA MTAM could be used as a suitable substrate for vascular engineering.

Influence of Vincristine, Clinically Used in Cancer Therapy and Immune Thrombocytopenia, on the Function of Human Platelets.

Vincristine is a clinically used antimicrotubule drug for treating patients with lymphoma. Due to its property of increasing platelet counts, vincristine is also used to treat patients with immune thrombocytopenia. Moreover, antiplatelet agents were reported to be beneficial in thrombotic thrombocytopenic purpura (TTP). Therefore, we investigated the detailed mechanisms underlying the antiplatelet effect of vincristine. Our results revealed that vincristine inhibited platelet aggregation induced by collagen, but not by thrombin, arachidonic acid, and the thromboxane A2 analog U46619, suggesting that vincristine exerts higher inhibitory effects on collagen-mediated platelet aggregation. Vincristine also reduced collagen-mediated platelet granule release and calcium mobilization. In addition, vincristine inhibited glycoprotein VI (GPVI) signaling, including Syk, phospholipase Cγ2, protein kinase C, Akt, and mitogen-activated protein kinases. In addition, the in vitro PFA-100 assay revealed that vincristine did not prolong the closure time, and the in vivo study tail bleeding assay showed that vincristine did not prolong the tail bleeding time; both findings suggested that vincristine may not affect normal hemostasis. In conclusion, we demonstrated that vincristine exerts antiplatelet effects at least in part through the suppression of GPVI signaling. Moreover, this property of antiplatelet activity of vincristine may provide additional benefits in the treatment of TTP.