Decentralized state estimation: An approach using pseudomeasurements and preintegration.

This paper addresses the problem of decentralized, collaborative state estimation in robotic teams. In particular, this paper considers problems where individual robots estimate similar physical quantities, such as each other's position relative to themselves. The use of pseudomeasurements is introduced as a means of modeling such relationships between robots' state estimates and is shown to be a tractable way to approach the decentralized state estimation problem. Moreover, this formulation easily leads to a general-purpose observability test that simultaneously accounts for measurements that robots collect from their own sensors, as well as the communication structure within the team. Finally, input preintegration is proposed as a communication-efficient way of sharing odometry information between robots, and the entire theory is appropriate for both vector-space and Lie-group state definitions. To overcome the need for communicating preintegrated covariance information, a deep autoencoder is proposed that reconstructs the covariance information from the inputs, hence further reducing the communication requirements. The proposed framework is evaluated on three different simulated problems, and one experiment involving three quadcopters.

Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT.

PURPOSE: Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES. METHODS: We conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping. RESULTS: In 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype-phenotype correlation. CONCLUSION: We conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.

Various types of electrochemical biosensors for leukemia detection and therapeutic approaches.

Leukemia often initiates following dysfunctions in hematopoietic stem cells lineages. Various types of leukemia, including acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), acute promyelocytic leukemia (APL), and human T-cell leukemia/lymphoma virus type 1 (HTLV-1) can thus call for different diagnosis and treatment options. One of the most important subjects in leukemia is the early detection of the disease for effective therapeutic purposes. In this respect, biosensors detecting the molecules of deoxyribonucleic acid (DNA) as analytes are called genosensors or DNA biosensors. Electrochemical sensors, as the most significant approach, also involve reacting of chemical solutions with sensors to generate electrical signals proportional to analyte concentrations. Biosensors can further help detect cancer cells in the early stages of the disease. Moreover, electrochemical biosensors, developed based on various nanomaterials (NMs), can increase sensitivity to the detection of leukemia-related genes, e.g., BCR/ABL as a fusion gene and promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα). Therefore, the present review reflects on previous studies recruiting different NMs for leukemia detection.

Whole exome sequencing identifies potential candidate genes for spina bifida derived from mouse models.

Spina bifida (SB) is the second most common nonlethal congenital malformation. The existence of monogenic SB mouse models and human monogenic syndromes with SB features indicate that human SB may be caused by monogenic genes. We hypothesized that whole exome sequencing (WES) allows identification of potential candidate genes by (i) generating a list of 136 candidate genes for SB, and (ii) by unbiased exome-wide analysis. We generated a list of 136 potential candidate genes from three categories and evaluated WES data of 50 unrelated SB cases for likely deleterious variants in 136 potential candidate genes, and for potential SB candidate genes exome-wide. We identified 6 likely deleterious variants in 6 of the 136 potential SB candidate genes in 6 of the 50 SB cases, whereof 4 genes were derived from mouse models, 1 gene was derived from human nonsyndromic SB, and 1 gene was derived from candidate genes known to cause human syndromic SB. In addition, by unbiased exome-wide analysis, we identified 12 genes as potential candidates for SB. Identification of these 18 potential candidate genes in larger SB cohorts will help decide which ones can be considered as novel monogenic causes of human SB.

Cancer combination therapies by angiogenesis inhibitors; a comprehensive review.

Abnormal vasculature is one of the most conspicuous traits of tumor tissue, largely contributing to tumor immune evasion. The deregulation mainly arises from the potentiated pro-angiogenic factors secretion and can also target immune cells' biological events, such as migration and activation. Owing to this fact, angiogenesis blockade therapy was established to fight cancer by eliminating the nutrient and oxygen supply to the malignant cells by impairing the vascular network. Given the dominant role of vascular-endothelium growth factor (VEGF) in the angiogenesis process, the well-known anti-angiogenic agents mainly depend on the targeting of its actions. However, cancer cells mainly show resistance to anti-angiogenic agents by several mechanisms, and also potentiated local invasiveness and also distant metastasis have been observed following their administration. Herein, we will focus on clinical developments of angiogenesis blockade therapy, more particular, in combination with other conventional treatments, such as immunotherapy, chemoradiotherapy, targeted therapy, and also cancer vaccines. Video abstract.

Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.

The main breakthrough in tumor immunotherapy was the discovery of immune checkpoint (IC) proteins, which act as a potent suppressor of the immune system by a myriad of mechanisms. After that, scientists focused on the immune checkpoint molecules mainly. Thereby, much effort was spent to progress novel strategies for suppressing these inhibitory axes, resulting in the evolution of immune checkpoint inhibitors (ICIs). Then, ICIs have become a promising approach and shaped a paradigm shift in tumor immunotherapies. CTLA-4 plays an influential role in attenuation of the induction of naïve and memory T cells by engagement with its responding ligands like B7-1 (CD80) and B7-2 (CD86). Besides, PD-1 is predominantly implicated in adjusting T cell function in peripheral tissues through its interaction with programmed death-ligand 1 (PD-L1) and PD-L2. Given their suppressive effects on anti-tumor immunity, it has firmly been documented that ICIs based therapies can be practical and rational therapeutic approaches to treat cancer patients. Nonetheless, tumor inherent or acquired resistance to ICI and some treatment-related toxicities restrict their application in the clinic. The current review will deliver a comprehensive overview of the ICI application to treat human tumors alone or in combination with other modalities to support more desired outcomes and lower toxicities in cancer patients. Video Abstract.

Apigenin alleviates resistance to doxorubicin in breast cancer cells by acting on the JAK/STAT signaling pathway.

BACKGROUND: Breast cancer is the most frequent cancer among women. Despite the effectiveness of Doxorubicin (DOX) as a chemotherapeutic for the treatment of breast cancer, the therapy-resistance remains unsolvable. Apigenin is a natural dietary flavonoid with potential anticancer activities. Our study's intention was to evaluate the effect of Apigenin on DOX resistance in MCF-7 cells. METHODS: DOX-resistant MCF-7 cell line (MCF-7R) was developed by treating MCF-7 cells with increasing concentrations of DOX (0-100 µM). The viability of cell lines was assayed using MTT method. Quantitative polymerase chain reaction method was performed to measure multidrug-resistance 1 (MDR1) gene expression level. The expression of MDR1, Janus kinase 2 (JAK2) and Signal transducer and activator of transcription 3 (STAT3) proteins were determined by western blotting. RESULTS: MCF-7R cell line showed resistance to DOX in comparison to MCF-7 cells. Apigenin had a significant effect on the reduction of viability of both MCF-7 and MCF-7R cell lines. However, DOX-resistance in the MCF-7 cell line was considerably decreased due to the co-treatment of MCF-7R cells with Apigenin. This natural compound also downregulated the expression of MDR1 at mRNA and protein levels both in resistant and non-resistant cells. Apigenin significantly prohibited the phosphorylation and activation of JAK2 and STAT3 proteins both in MCF-7 and MCF-7R cell lines. CONCLUSIONS: The present results suggested, for the first time, Apigenin as an ideal therapeutic for ameliorating DOX resistance in breast cancer. These data also proposed a novel mechanism for the anti-resistance activity of Apigenin by regulating the JAK2/STAT3/MDR1 axis.

The role of Pycnogenol in the control of inflammation and oxidative stress in chronic diseases: Molecular aspects.

The prevalence of chronic diseases has increased significantly with the rising trend of sedentary lifestyles, reduced physical activity, and dietary modifications in recent decades. Inflammation and oxidative stress play a key role in the pathophysiology of several chronic diseases, such as type II diabetes, cardiovascular diseases, and hepatic conditions. Therefore, reducing inflammation and oxidative stress may be beneficial in the prevention and treatment of various chronic disorders. Since chronic diseases are not completely curable, various methods have been proposed for their control. Complementary therapies and the use of natural antioxidant and antiinflammatory compounds are among these novel approaches. Pycnogenol (PYC) is a natural compound that could control inflammation and oxidative stress. Furthermore, some previous studies have shown that PYC could effectively reduce inflammation through signaling the downstream of insulin receptors, inhibiting the phosphorylation of the serine residues of insulin receptor substrate-1, reducing pro-inflammatory cytokines and oxidative stress indices through the stimulation of antioxidant pathways, increasing free radical scavenging activities, preventing lipid peroxidation, and protecting the erythrocytes in glucose-6-phosphate dehydrogenase-deficient individuals, although these effects have not been fully proved. The present study aimed to comprehensively review the evidence concerning the positive physiological and pharmacological properties of PYC, with an emphasis on the therapeutic potential of this natural component for enhancing human health.

Corrigendum to ``Protective Role of Sarpogrelate in Combination with Bromocriptine and Cabergoline for Treatment of Diabetes in Alloxan-induced Diabetic Rats'' [Current Therapeutic Research Volume 95, 2021, 100647].

[This corrects the article DOI: 10.1016/j.curtheres.2021.100647.].

Homozygous WNT9B variants in two families with bilateral renal agenesis/hypoplasia/dysplasia.

WNT9B plays a key role in the development of the mammalian urogenital system. It is essential for the induction of mesonephric and metanephric tubules, the regulation of renal tubule morphogenesis, and the regulation of renal progenitor cell expansion and differentiation. To our knowledge, WNT9B has not been associated with renal defects in humans; however, WNT9B-/- mice have renal agenesis/hypoplasia and reproductive tract abnormalities. We report four individuals from two unrelated consanguineous families with bilateral renal agenesis/hypoplasia/dysplasia and homozygous variants in WNT9B. The proband from Family 1 has bilateral renal cystic dysplasia and chronic kidney disease. He has two deceased siblings who presented with bilateral renal hypoplasia/agenesis. The three affected family members were homozygous for a missense variant in WNT9B (NM_003396.2: c.949G>A/p.(Gly317Arg)). The proband from Family 2 has renal hypoplasia/dysplasia, chronic kidney disease, and is homozygous for a nonsense variant in WNT9B (NM_003396.2: c.11dupC/p.(Pro5Alafs*52)). Two of her siblings died in the neonatal period, one confirmed to be in the context of oligohydramnios. The proband's unaffected brother is also homozygous for the nonsense variant in WNT9B, suggesting nonpenetrance. We propose a novel association of WNT9B and renal anomalies in humans. Further study is needed to delineate the contribution of WNT9B to genitourinary anomalies in humans.

Incidence and Outcome of Community-Acquired Acute Kidney Injury in Pediatric Patients Seen at an Emergency Department: A Retrospective Cohort Study.

OBJECTIVES: Acute kidney injury (AKI) has significant morbidity and mortality rates among young patients. This study aimed to determine the incidence and outcome of community-acquired AKI among pediatric patients seen in the emergency department of King Abdulaziz University Hospital for more than 3 years. METHODS: This retrospective study reviewed electronic medical records for all pediatric patients aged 1 month to 18 years who visited the emergency department of King Abdulaziz University Hospital from January 1, 2015, until December 31, 2017. Acute kidney injury was diagnosed and classified according to the Kidney Disease: Improving Global Outcomes criteria. RESULTS: Of 6038 patients, 1581 were included. Acute kidney injury occurred in 135 patients (8.5%), of which 77 (57%) were in stage 1, 42 (31.1%) were in stage 2, and 16 (11.9%) were in stage 3. Mortality was higher in the AKI group (4.4%) than in the non-AKI group (0.2%; P < 0.01). On long-term observation, 14.8% did not return for follow-up, 58.5% of survivors recovered completely, and 22.2% progressed to chronic kidney disease. The most affected age group was 1 month to 2 years (26%). Common admission causes were chemotherapy-induced AKI (31.9%) and pneumonia (10.4%). There was a significant inverse relationship between AKI and age group (P < 0.001) and a positive association between AKI and death (P < 0.001). However, no association was found between AKI stages and outcomes. CONCLUSIONS: Community-acquired AKI remains a common condition affecting the pediatric population. It is associated with a higher mortality rate. Infants were more susceptible to AKI, and a significant number of patients with AKI progressed to chronic kidney disease.

Protective Role of Sarpogrelate in Combination with Bromocriptine and Cabergoline for Treatment of Diabetes in Alloxan-induced Diabetic Rats.

BACKGROUND: Although dopamine D2 receptor agonists, bromocriptine and cabergoline, are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia, there is an identified relationship between the utilization of D2-like R agonists and the progress of myocardial injury, especially in the early phase of therapy. OBJECTIVE: This investigation aimed to examine the potential activity of sarpogrelate (a 5-hydroxytryptamine 2A [5-HT2A] receptor blocker) in reducing myocardial injury prompted by extended haul utilization of D2 receptor agonists in a model of diabetic rats. METHODS: In the in vivo studies, both bromocriptine and cabergoline were managed independently and combined with sarpogrelate for about a month in diabetic nephropathy rats. Blood glucose level and other myocardial biochemical parameters were estimated. The probable mechanism for insulin secretagogue action was evaluated through in vitro isolated islets study. Sodium/potassium-adenosine triphosphatase activity was assayed in an isolated microsomal fraction of the renal cortex. Isolated perfused rat hearts were treated with different doses of dopamine before and after being subjected to the tested drugs, dose response of heart rate, and heart contractility were recorded. RESULTS: Bromocriptine and cabergoline created a significant reduction in blood glucose level without any action on insulin secretagogues. Bromocriptine prevented the loss of sodium/potassium-adenosine triphosphatase activity in the cortex of an ischemic kidney. Treatment of bromocriptine or cabergoline with sarpogrelate altogether decreased the levels of the elevated myocardial biomarkers in serum. Administration of different doses of dopamine in presence of bromocriptine or capergoline resulted in significantly rising in the heart rate percentage comparing to dopamine alone. A mix of bromocriptine or cabergoline with sarpogrelate diminished both heart rate and contractility, respectively. CONCLUSIONS: The examination demonstrated that the combined use of sarpogrelate with bromocriptine or cabergoline decreased the potential adverse effects of these 2 drugs on myocardial tissues.

Serum cystatin is a useful marker for the diagnosis of acute kidney injury in critically ill children: prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) has been associated with high morbidity and mortality rates among critically ill children. Cystatin C is a protease inhibitor, and studies have shown that it is a promising marker for the early diagnosis of AKI. Our goal in this study was to assess whether serum cystatin C could serve as an accurate marker for the diagnosis of AKI. METHODS: This prospective study was undertaken in the pediatric intensive care unit at King Abdulaziz University Hospital. Serum creatinine and serum cystatin C levels were both measured in patients on admission (0 h) and at 6, 12, and 24 h after admission. AKI was diagnosed according to the modified pRIFLE criteria. Receiver operating characteristic (ROC) curve analysis was performed to assess the utility of serum cystatin C for diagnosing AKI. RESULTS: A total of 62 patients were enrolled in this study, and 32 were diagnosed with AKI according to the modified pRIFLE criteria (51.4 %). The area under the ROC curve for serum cystatin indicated that it was a good marker for the diagnosis of AKI at 0, 6, 12 and 24 h, with sensitivities of 78, 94, 94 and 83 %, respectively. However, the specificities of serum cystatin C at 0, 6, 12, and 24 h were 57, 57, 60 and 50 %, respectively. The optimal cutoff value was 0.645 mg/L. The area under the ROC for serum creatinine showed sensitivities of 50, 65.4, 69.2 and 57.7 % and specificities of 67.7, 70, 60 and 70 % at 0, 6, 12 and 24 h, respectively. The optimal cutoff value for serum creatinine was 30 µmol/l. Comparisons of ROC curves revealed that serum cystatin C was superior to serum creatinine for the diagnosis of AKI at 12 h (p = 0.03), but no differences were detected at 0, 6 or 24 h. CONCLUSION: Serum cystatin is a sensitive, but not a specific, marker for the diagnosis of AKI in critically ill children.

Outcome of acute kidney injury in pediatric patients admitted to the intensive care unit.

BACKGROUND: Acute kidney injury (AKI) is common in the pediatric intensive care unit (PICU). We aimed to describe the etiology, clinical features, and outcome of AKI in pediatric patients and to determine the predictors for initiation of renal replacement and mortality. METHODS: A retrospective chart review was performed of the medical records for all patients who were admitted to the PICU at King Abdulaziz University Hospital between January 1 and December 31, 2011. The pediatric-modified RIFLE criteria were used to classify AKI. RESULTS: We included 102 children with AKI, aged 4 - 60 months. Oliguria (61.5%, p < 0.0001) and hypervolemic signs (38.5%, p = 0.03) were more common among patients with RIFLE class failure. They also had the highest mortality (53.9%, p = 0.01). Oliguric patients were ~ 23 times more likely than their non-oliguric counterparts to be initiated on renal replacement therapy (RRT) (RR = 23.38, 95% CI: 3.07 - 178.16). Diuretic infusion was also a strong predictor for RRT initiation (RR = 10.00, 95% CI: 2.77 - 36.12). Hypervolemic patients were twice more likely to die during hospitalization in both unadjusted and adjusted models (RR = 2.06, 95% CI: 1.09 - 3.90, and aRR = 2.45, 95% CI: 1.09 - 5.51, respectively). Mechanical ventilation and RRT initiation were associated with higher likelihood of death (ARR = 13.23, 95% CI: 1.90 - 92.04, and ARR = 2.20, 95% CI: 1.18 - 4.12, respectively). Patients with RIFLE class Failure were about thrice more likely than patients with RIFLE class Risk to die in both the unadjusted (RR = 2.76, 95% CI: 1.35 - 5.65), and adjusted models (ARR = 2.88, 95% CI: 1.38 - 6.04). Children with AKI had longer PICU stay (0.0003) and higher mortality (< 0.0001) than the non-AKI group. CONCLUSION: Severe AKI predicted high mortality in critically ill children.

Data reduction for SVM training using density-based border identification.

Numerous classification and regression problems have extensively used Support Vector Machines (SVMs). However, the SVM approach is less practical for large datasets because of its processing cost. This is primarily due to the requirement of optimizing a quadratic programming problem to determine the decision boundary during training. As a result, methods for selecting data instances that have a better likelihood of being chosen as support vectors by the SVM algorithm have been developed to help minimize the bulk of training data. This paper presents a density-based method, called Density-based Border Identification (DBI), in addition to four different variations of the method, for the lessening of the SVM training data through the extraction of a layer of border instances. For higher-dimensional datasets, the extraction is performed on lower-dimensional embeddings obtained by Uniform Manifold Approximation and Projection (UMAP), and the resulting subset can be repetitively used for SVM training in higher dimensions. Experimental findings on different datasets, such as Banana, USPS, and Adult9a, have shown that the best-performing variations of the proposed method effectively reduced the size of the training data and achieved acceptable training and prediction speedups while maintaining an adequate classification accuracy compared to training on the original dataset. These results, as well as comparisons to a selection of related state-of-the-art methods from the literature, such as Border Point extraction based on Locality-Sensitive Hashing (BPLSH), Clustering-Based Convex Hull (CBCH), and Shell Extraction (SE), suggest that our proposed methods are effective and potentially useful.

Evaluation of the impact of different disinfectants on new coronavirus and human health.

A new health threat was appeared in 2019 known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19). The new coronavirus distributed all over the world and caused millions of deaths. One way to incomplete the process of COVID-19 transfer from one person to another is using disinfectants. A narrative review study was done on manuscript published documents about the stability of the virus, different types of disinfectants and the effects of disinfectants on SARS-CoV2 and environment from 2005 to 2022 based on Searched databases included Google Scholar, Springer, PubMed, Web of Science and Science Direct (Scopus). All relevant studies published 2005 until 2022 gathered. According to the databases, 670 articles were retrieved. Thirty studies were screened after review and 30 full-text articles entered into the analysis process. Finally, 14 articles were selected in this study. New coronavirus could survive until 9 days in room temperature; the surviving time decreases if temperature increases. The virus can survive in various plastic, glass, and metal surfaces for hours to days. Disinfectants, such as alcohol, isopropanol, formaldehyde, glutaraldehyde, and ethanol, can kill 70-90% viruses in up to 30 s but should be noted that these disinfectants are recognized by Occupational Safety and Health Administration (OSHA) as a potential carcinogen. According to the different reports, increased duration and level of disinfectant exposure can have negative impacts on human and animal health including upper and lower respiratory tract irritation, inflammation, edema, ulceration, and allergic reactions.

The effect of conjugated linoleic acids on inflammation, oxidative stress, body composition and physical performance: a comprehensive review of putative molecular mechanisms.

Conjugated linoleic acids (CLAs) are polyunsaturated fatty acids primarily found in dairy products and ruminant animal products such as beef, lamb, and butter. Supplementation of CLAs has recently become popular among athletes due to the variety of health-promoting effects, including improvements in physical performance. Preclinical and some clinical studies have shown that CLAs can reduce inflammation and oxidative stress and favorably modulate body composition and physical performance; however, the results of previously published clinical trials are mixed. Here, we performed a comprehensive review of previously published clinical trials that assessed the role of CLAs in modulating inflammation, oxidative stress, body composition, and select indices of physical performance, emphasizing the molecular mechanisms governing these changes. The findings of our review demonstrate that the effect of supplementation with CLAs on inflammation and oxidative stress is controversial, but this supplement can decrease body fat mass and increase physical performance. Future well-designed randomized clinical trials are warranted to determine the effectiveness of (1) specific doses of CLAs; (2) different dosing durations of CLAs; (3) various CLA isomers, and the exact molecular mechanisms by which CLAs positively influence oxidative stress, inflammation, body composition, and physical performance.

Vitamin D and Swimming Exercise Prevent Obesity in Rats under a High-Fat Diet via Targeting FATP4 and TLR4 in the Liver and Adipose Tissue.

The prevalence of obesity has risen in the last decades, and it has caused massive health burdens on people's health, especially metabolic and cardiovascular issues. The risk of vitamin D insufficiency is increased by obesity, because adipose tissue alters both the requirements for and bioavailability of vitamin D. Exercise training is acknowledged as having a significant and long-term influence on body weight control; the favorable impact of exercise on obesity and obesity-related co-morbidities has been demonstrated via various mechanisms. The current work illustrated the effects of vitamin D supplementation and exercise on obesity induced by a high-fat diet (HFD) and hepatic steatosis in rats and explored how fatty acid transport protein-4 (FATP4) and Toll-like receptor-4 antibodies (TLR4) might be contributing factors to obesity and related hepatic steatosis. Thirty male albino rats were divided into five groups: group 1 was fed a normal-fat diet, group 2 was fed an HFD, group 3 was fed an HFD and given vitamin D supplementation, group 4 was fed an HFD and kept on exercise, and group 5 was fed an HFD, given vitamin D, and kept on exercise. The serum lipid profile adipokines, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were analyzed, and the pathological changes in adipose and liver tissues were examined. In addition, the messenger-ribonucleic acid (mRNA) expression of FATP4 and immunohistochemical expression of TLR4 in adipose and liver tissues were evaluated. Vitamin D supplementation and exercise improved HFD-induced weight gain and attenuated hepatic steatosis, along with improving the serum lipid profile, degree of inflammation, and serum adipokine levels. The expression of FATP4 and TLR4 in both adipose tissue and the liver was downregulated; it was noteworthy that the group that received vitamin D and was kept on exercise showed also improvement in the histopathological picture of this group. According to the findings of this research, the protective effect of vitamin D and exercise against obesity and HFD-induced hepatic steatosis is associated with the downregulation of FATP4 and TLR4, as well as a reduction in inflammation.

Application of extracellular vesicles derived from mesenchymal stem cells as potential therapeutic tools in autoimmune and rheumatic diseases.

Mesenchymal stem cells (MSCs) have been proven to have superior potential to be used astherapeutic candidates in various disorders. Nevertheless, the clinical application of these cells have been restricted because of their tumorigenic properties. Increasing evidence has established that the valuable impacts of MSCs are mainly attributable to the paracrine factors including extracellular vesicles (EVs). EVs are nanosized double-layer phospholipid membrane vesicles contain various proteins, lipids and miRNAs which mediate cell-to-cell communications. Due to their inferior immunogenicity and tumorigenicity, as well as easier management, EVs have drawn attention as potential cell-free replacement therapy to MSCs. For that reason, herein, we reviewed the recent findings of researches on different MSC-EVs and their effectiveness in the treatment of several autoimmune and rheumatic diseases including multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, osteoporosis, and systemic lupus erythematosus as well as Sjogren's syndrome, systemic sclerosis and other autoimmune diseases.

Mesenchymal stromal/stem cells and their exosomes application in the treatment of intervertebral disc disease: A promising frontier.

Today, the application of mesenchymal stromal/stem cells (MSCs) and their exosomes to treat degenerative diseases has received attention. Due to the characteristics of these cells, such as self-renewability, differentiative and immunomodulatory effects, their use in laboratory and clinical studies shows promising results. However, the allogeneic transplantation problems of MSCs limit the use of these cells in the clinic. Scientists propose the application of exosomes to use from the therapeutic effect of MSCs and overcome their defects. These vesicles change the target cell behaviour and transcription profile by transferring various cargo such as proteins, mi-RNAs, and lipids. One of the degenerative tissue diseases in which MSCs and their exosomes are used in their treatment is intervertebral disc disease (IDD). Different factors such as genetics, nutrition, ageing, and environmental factors play a significant role in the onset and progression of this disease. These factors affect the cellular and molecular properties of the disc, leading to tissue destruction. Nucleus pulposus cells (NPCs) are among the most important cells involved in the pathogenesis of disc degeneration. MSCs exert their therapeutic effects by differentiating, reducing apoptosis, increasing proliferation, and decreasing senescence in NPCs. In addition, the use of MSCs and their exosomes also affects the annulus fibrosus and cartilaginous endplate cells in disc tissue and prevents disc degeneration progression.