Exosomes, 60-200-nm extracellular vesicles secreted from cells, have been used as an active pharmaceutical ingredient or drug carrier in disease treatment. Human- and plant-derived exosomes are registered in clinical trials, but more complete reports are available for human-derived exosomes. Because exosomes act as vesicles and carry cell secreting components, they have been used as drug or peptide vehicles to treat diseases. The dendritic cells (DCs) and mesenchymal stem cells (MSCs) are two popular cell sources for exosome preparation. Exosomes from DCs can initiate inflammation in patients, particularly in patients with cancer, as they contain the tumor antigen to induce specific inflammation response. A well-established cell bank of MSCs is available, and these cells can be used as an alternative source for exosome preparation. The major application of MSC-derived exosomes is in inflammation treatment. Exosomes in clinical trials need to comply with good manufacturing practice (GMP). Three important issues are prevalent in GMP for exosomes, i.e., upstream of cell cultivation process, downstream of the purification process, and exosome quality control. This paper concisely reviews exosome development, including exosome generation and clinical trial application.

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Ovarian torsion is a rare but emergency condition in women. Early diagnosis is necessary to preserve the function of the ovaries and tubes and prevent severe morbidity. Ovarian torsion refers to complete or partial rotation of the adnexal supporting organ with ischemia. It can affect females of all ages. Ovarian torsion occurs in around 2%–15% of patients who have surgical treatment of adnexal masses. The main risk in ovarian torsion is an ovarian mass. The most common symptom of ovarian torsion is acute onset of pelvic pain, followed by nausea and vomiting. Pelvic ultrasonography can provide information on ovarian cysts. Once ovarian torsion is suspected, surgery or detorsion is the mainstay of diagnosis and treatment.

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Acute myocardial ischemia/reperfusion (I/R) injury is a significant, unsolved clinical puzzle. In the disease context of acute myocardial infarction, reperfusion remains the only effective strategy to salvage ischemic myocardium, but it also causes additional damage. Myocardial I/R injury is composed of four types of damage, and these events attenuate the benefits of reperfusion therapy. Thus, inventing new strategies to conquer I/R injury is an unmet clinical need. A variety of pathological processes and mediators, including changes in the pH, generation of reactive oxygen radicals, and intracellular calcium overload, are proposed to be crucial in I/R-related cell injury. Among the intracellular events that occur during I/R, we stress the importance of protein phosphorylation signaling and elaborate its regulation. A variety of protein kinase pathways could be activated in I/R, including reperfusion injury salvage kinase and survivor-activating factor enhancement pathways, which are critical to cardiomyocyte survival. In addition to serine/threonine phosphorylation signaling, protein tyrosine phosphorylation is also critical in multiple cell functions and survival. However, the roles of protein kinases and phosphatases in I/R have not been extensively studied yet. By better understanding the mechanisms of I/R injury, we may have a better chance to develop new strategies for I/R injury and apply them in the clinical patient care.

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Leptin is a 167-amino-acid protein released by white adipose tissue and encoded by the obese gene. It has a role as a negative regulator of appetite control through sending a satiety signal to act on receptors within the hypothalamus. At normal levels, leptin can exert its effects on weight regulation according to white fat mass, induce sodium excretion, maintain vascular tone, and repair the myocardium. Beyond these effects, elevated serum leptin levels have been implicated in the pathogenesis of metabolic syndrome, diabetes mellitus, hypertension, and multiple cardiovascular diseases. In addition, hyperleptinemia had been reported to contribute to renal diseases through multiple mechanisms resulting in glomerulopathy presenting with a decreased glomerular filtration rate, increased albuminuria, and related clinical symptoms, which are pathophysiological features of chronic kidney disease. Because these cardiovascular and metabolic disorders are great challenges for physicians, understanding the related pathophysiological association with leptin might become a valuable aid in handling patients in daily clinical practice. This review will discuss the roles of leptin in the regulation of biological functions of multiple organs beyond the maintenance of feeding and metabolism.

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Recurrent urinary tract infection (UTI) might be one of the most common problems in urological clinics. Recent research has revealed novel evidence about recurrent UTI and it should be considered a different disease from the first infection. The pathogenesis of recurrent UTI might include two mechanisms, bacterial factors and deficiencies in host defense. Bacterial survival in the urinary bladder after antibiotic treatment and progression to form intracellular bacterial communities might be the most important bacterial factors. In host defense deficiency, a defect in pathogen recognition and urothelial barrier function impairment play the most important roles. Immunodeficiency and urogenital tract anatomical abnormalities have been considered the essential risk factors for recurrent UTI. In healthy women, voiding dysfunction and behavioral factors also increase the risk of recurrent UTI. Sexual intercourse and estrogen deficiency in postmenopausal women might have the strongest association with recurrent UTI. Traditional lifestyle factors such as fluid intake and diet are not considered independent risk factors now. Serum and urine biomarkers to predict recurrent UTI from the first infection have also attracted a wide attention recently. Current clinical evidence suggests that serum macrophage colony-stimulating factor and urinary nerve growth factor have potential predictive value for recurrent UTI. Clinical trials have proven the efficacy of the oral immunoactive agent OM-89 for the prevention of UTI. Vaccines for recurrent UTI are recommended by the latest guidelines and are available on the market.

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Objectives: Osteoarthritis (OA) is a chronic disease of degenerative joints. Mesenchymal stem cells (MSCs) have been used for cartilage regeneration in OA. We investigated the therapeutic potential of human umbilical cord-derived MSCs (HUCMSCs) with hyaluronic acid (HA) hydrogel transplanted into a porcine OA preclinical model. Materials and Methods: The HUCMSCs were characterized with respect to morphology, surface markers, and differentiation capabilities. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to examine gene expressions in a HUCMSC–HA coculture. Two healthy female minipigs weighing 30–40 kg and aged approximately 4 months were used in this large animal study. A full-thickness chondral injury was created in the trochlear groove of each of the pig's rear knees. After 3 weeks, a second osteochondral defect was created. Then, 1.5 mL of a HUCMSC (5 × 10⁶ cells) and HA composite (4%) was transplanted into the chondral-injured area in the right knee of each pig. Using the same surgical process, an osteochondral defect (untreated) was created in the left knee as a control. The pigs were sacrificed 12 weeks after transplantation. Macroscopic and microscopic histologies, qRT-PCR, and immunostaining evaluated the degree of chondral degradation. Results: The HUCMSCs exhibited typical MSC characteristics, including spindle morphology, expression of surface markers (positive for CD29, CD4, CD73, CD90, and human leukocyte antigen [HLA]-ABC; negative for CD34, CD45, and HLA-DR), and multipotent differentiation (adipogenesis, osteogenesis, and chondrogenesis). More extensive proliferation of HUCMSCs was noted with 4% and 25% of HA than without HA. Expression of COL2A1 and aggrecan in the HUCMSC-derived chondrocytes was increased when HA was included. The treated knees showed significant gross and histological improvements in hyaline cartilage regeneration when compared to the control knees. The International Cartilage Repair Society histological score was higher for the treated knees than the control knees. Conclusion: Our findings suggest that cartilage regeneration using a mixture of HUCMSCs and HA in a large animal model may be an effective treatment for OA, and this study is a stepping stone toward the future clinical trials.

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Alzheimer's disease (AD) and osteoporosis are both common degenerative diseases in the elderly population. The incidence of both diseases increases with age and will be posing enormous societal burden worldwide. It may appear that AD and osteoporosis are two distinct diseases although many risk factors are shared. Previous observational studies have shown that patients with osteoporosis have higher risks of developing AD than those who do not have osteoporosis. Although osteoporosis, falls, and fractures are more often seen in patients with AD than other older adults, the association between these two diseases may be due to a pathophysiological link rather than one condition causing the other. Several in vitro and in vivo studies lend support to this notion. Patients with AD have excessive amyloid plaques in the brain, and the pathology may extend to peripheral organs and cause skeletal amyloid deposition, which would enhance receptor activator nuclear factor-kappa B ligand signaling and lead to greater osteoclast activities. Patients with osteoporosis may have Vitamin D deficiency or lower levels of Vitamin D binding protein, which protects against amyloid aggregation, thus linking Vitamin D deficiency and AD or osteoporosis and AD. Osteoporosis coexisting with AD provides a window to examine the amyloid hypothesis from peripheral tissues. Future studies are warranted to clarify the role of genetic background regarding Vitamin D levels, exposure to sunlight, estrogen replacement therapy, and physical activity in patients with both chronic diseases.

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Good medical leadership is the key to building high-quality healthcare. However, in the development of medical careers, the teaching of leadership has traditionally not equaled that of technical and academic competencies. As a result of changes in personal standards, the quality of medical leadership has led to variations between different organizations, as well as occasional catastrophic failure in the standard of care provided for patients. Leaders in the medical profession have called for reform in healthcare in response to challenges in the system and improvements in public health. Furthermore, there has been an increased drive to see leadership education for doctors starting earlier, and continuing throughout their careers so that they can take on more important leadership roles throughout the healthcare system. Being a physician requires not only management and leadership but also the need to transfer competencies to communication and critical thinking. These attributes can be obtained through experience in teamwork under the supervision of teaching staff. Therefore, medical students are expected to develop skills to deal with and resolve conflicts, learn to share leadership, prepare others to help and replace them, take mutual responsibility and discuss their performance.

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Objective: Carbapenems are effective agents to treat multidrug-resistant (MDR) strains of bacteria, including Pseudomonas aeruginosa. However, there is a potential threat of emergence of carbapenem-resistant P. aeruginosa (CRPA). The aim of this study was to determine antibiotic susceptibility patterns and metallo-beta-lactamase (MBL)-mediated resistance in clinical P. aeruginosa isolates. Materials and Methods: Different clinical specimens were subjected to conventional culture-based identification of P. aeruginosa. Antimicrobial susceptibility patterns and MBL production were evaluated using the Kirby-Bauer and combined double-disk synergy test methods, respectively. Multiplex polymerase chain reaction was performed to investigate the presence of the bla_IMP, bla_VIM, bla_NDM, bla_SPM, and bla_SIMgenes. Results: A total of 71 clinical P. aeruginosa isolates were recovered, of which 28.17% were identified as CRPA. The most active antibiotics were colistin and polymyxin B (92.96% susceptibility to each). A total of 35% and 50% of CRPA isolates were MDR and extensively drug-resistant (XDR), respectively. MBL activity was shown in 20% of CRPA. A total of 90%, 40%, and 5% of CRPA isolates harbored the bla_IMP, bla_VIM, and bla_NDMgenes, respectively. No correlation was found between the MBL-encoding genes of P. aeruginosa and patient characteristics. Conclusion: Although the prevalence of CRPA in our therapeutic centers was relatively low, this rate of carbapenem resistance reflects a threat limiting treatment choices. A high prevalence of MDR/XDR phenotypes among the MBL-producer isolates suggests the need for continuous assessment of antimicrobial susceptibility and surveillance of antibiotic prescription. In addition, infection control measures are needed to prevent further dissemination of these organisms.

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Improving patient survival and quality of life in chronic diseases requires prolonged and often lifelong medication intake. Less than half of patients with chronic diseases globally are adherent to their prescribed medications which preclude the full benefit of treatment, worsens therapeutic outcomes, accelerates disease progression, and causes enormous economic losses. The accurate assessment of medication adherence is pivotal for both researchers and clinicians. Medication adherence can be assessed through both direct and indirect measures. Indirect measures include both subjective (self-report measures such as questionnaire and interview) and objective (pill count and secondary database analysis) measures and constitute the mainstay of assessing medication adherence. However, the lack of an inexpensive, ubiquitous, universal gold standard for assessment of medication adherence emphasizes the need to utilize a combination of measures to differentiate adherent and nonadherent patients. The global heterogeneity in health systems precludes the development of a universal guideline for evaluating medication adherence. Methods based on the secondary database analysis are mostly ineffectual in low-resource settings lacking electronic pharmacy and insurance databases and allowing refills without updated, valid prescriptions from private pharmacies. This significantly restricts the choices for assessing adherence until digitization of medical data takes root in much of the developing world. Nevertheless, there is ample scope for improving self-report measures of adherence. Effective interview techniques, especially accounting for suboptimal patient health literacy, validation of adherence questionnaires, and avoiding conceptual fallacies in reporting adherence can improve the assessment of medication adherence and promote understanding of its causal factors.

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So far, lots of analyses have been conducted to invent the appropriate therapeutic targets for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The category and the strategies for treating the virus are described in this review together with mentioning some specific drugs. Of them, saikosaponin possesses affinity of the drug toward nonstructural protein 15 and the spike glycoprotein of the SARS-CoV-2. The nucleotide inhibitors such as sofosbuvir, ribavirin, galidesivir, remdesivir, favipiravir, cefuroxime, tenofovir, and hydroxychloroquine (HCHL), setrobuvir, YAK, and IDX-184 were found to be effective in binding to SARS-CoV-2 RNA-dependent RNA polymerase. From the antimalarial and anti-inflammatory category, chloroquine and its derivative HCHL have already been approved by the U.S. Food and Drug Administration for emergency treatment of SARS-CoV-2 infection. The other drugs such as favipiravir and lopinavir/ritonavir under the antiviral category, the angiotensin-converting enzyme 2 (the renin-angiotensin system inhibitors), remdesivir (RNA polymerase inhibitor) from antiviral category, cepharanthine from anti-inflammatory category, etc., have been pointed based on the previous literature published. Besides, the assessment of the drug repositioning candidates with the related targets is also significant for the viral mitigation.

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Numerous studies indicate that microbiota plays an important role in human health. Diet is a factor related to microbiota which also influences human health. The relationships between diet, microbiota, and human health are complex. This review focuses on the current literature on vegan diets and their unique impact on gut microbiota. We also report on the health benefits of a vegan diet for metabolic syndrome, cardiovascular disease, and rheumatoid arthritis concerning relevant impacts from gut microbiota. Despite evidence supporting the clinical relevance of vegan gut microbiota to human health, the whole mechanism awaits further investigation.

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Objectives: Vegetarian diets have been shown to improve insulin resistance and reduce body weight, but the effects on nonalcoholic fatty liver require further confirmation. We aim to investigate the association between vegetarian diets, major food groups, and nonalcoholic fatty liver, and to compare the degree of liver fibrosis between vegetarians and nonvegetarians in those with fatty liver. Materials and Methods: We analyzed cross-sectional data from the Tzu Chi Health Study which included 2127 nonvegetarians and 1273 vegetarians who did not smoke or habitually drink alcohol and had no hepatitis B or hepatitis C. Fatty liver and liver fibrosis were determined using ultrasonography and the nonalcoholic fatty liver disease fibrosis score, respectively. Diet was assessed through a validated food frequency questionnaire. Results: Vegetarian diets were associated with lower odds of fatty liver (odds ratio = 0.79, 95% confidence interval: 0.68–0.91) after adjusting for age, gender, education, history of smoking and alcohol drinking. Adjustment for body mass index (BMI) attenuated the protective association. Vegetarians had less severe fibrosis than nonvegetarians. Replacing a serving of soy with a serving of meat or fish was associated with 12%–13% increased risk, and replacing a serving of whole grains with a serving of refined grains, fruits, and fruit juice was associated with 3%–12% increased the risk of fatty liver. Conclusion: Vegetarian diets, replacing meat and fish with soy, and replacing refined carbohydrates with whole grains, may be inversely associated with nonalcoholic fatty liver related to BMI.

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Objective: The mode of delivery in breech presentation (BP) is controversial. Several studies have reported the advantages and disadvantages of delivery mode in BP. The aim of this study was to compare the Apgar scores in BPs between vaginal and cesarean delivery. Materials and Methods: A retrospective study was conducted at Dr. Zainoel Abidin General Hospital from January 2010 to December 2012. Data on the mode of delivery and Apgar scores at 1 and 5 min for infants with a BP were extracted from the medical records. Logistic regression was employed to assess the correlation between mode of delivery and Apgar scores. In addition, a meta-analysis was conducted to summarize findings from other regions. Results: A total of 205 (3.9%) BPs among 5252 deliveries between January 2010 and December 2012 were analyzed for this study. There were 26% (52 cases) vaginal and 74% (153 cases) cesarean deliveries. The mode of delivery for BP had a significant association with Apgar score at 1 min (odds ratio [OR] 95% confidence interval [CI] = 6.462 [2.476–16.870], P = 0.0001) and 5 min (OR 95% CI =7.727 [1.416–42.175], P = 0.018). Our meta-analysis showed that the delivery mode had a significant association with Apgar score in BP (OR: 3.69; 95% CI: 2.18–6.26, P = 0.0001). Conclusions: There was a significant association between Apgar scores in BPs and mode of delivery. Our results suggest better outcomes for cesarean than vaginal delivery in BPs.

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Objectives: The objective of this study is to determine the effect of hemodialysis on the hearing threshold in patients with chronic renal failure (CRF). Materials and Methods: Fifty-nine patients with CRF on regular hemodialysis were followed up for 1 year with a pure-tone audiometric examination every 6 months. Results: The mean age of the patients was 41.8 ± 9.2 years (range: 17–50 years). At the beginning of the study, 39 patients (66.1%) had sensorineural hearing loss (SNHL). During the 12-month follow-up, 6 more patients developed SNHL giving a point prevalence rate of 76.3% at the end of the study. The hearing loss was more evident in the higher frequencies. Of the studied patients, 64.4% showed deterioration of the hearing threshold. The mean hearing threshold at the beginning of the study was 29.2 ± 21.1 dB versus 36.9 ± 17.3 dB at the end of the study (P < 0.001). No significant relation was found between age, sex, serum electrolytes, blood urea, and duration of CRF and hearing loss. Multivariate analysis showed that the duration of hemodialysis was the only significant independent predictor of SNHL. Conclusion: SNHL is common in patients with CRF on hemodialysis. It was mild to moderate in the majority of patients. Hearing impairment was most obvious at the high frequencies. Most of the patients showed further deterioration in the hearing threshold with the duration of dialysis.

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Mirtazapine (MTZ) is an atypical antidepressant approved by the FDA, which mechanism of action involves the antagonism of alpha-2, H1, 5-HT2A, 5-HT2C, and 5-HT3 receptors. In this context, the aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of MTZ-associated movement disorders (MDs). Relevant reports of six databases were identified and assessed by two reviewers without language restriction. Fifty-two reports containing 179 cases from 20 countries were assessed. The mean age was 57 year (range, 17–85). The majority of the individuals were female (60%) and of European origin. The mean time from MTZ start to symptom onset was 7.54 days; the time from management to MD improvement was within one week in 82.60% of the individuals. The MDs associated with MTZ were 69 restless legs syndrome (RLS), 35 tremors, 10 akathisia (AKT), 9 periodic limb MD, 6 dystonia, 4 rapid eye movement sleep behavior disorders, 3 dyskinesia, 2 parkinsonism, and 1 tic, and in the group not clearly identified, 18 restlessness, 15 hyperkinesis, and 1 extrapyramidal symptom. In the literature, the majority of the reports lack important information about the neurological examination. The management should be the MTZ withdrawal, except in RLS that other options are possible. In AKT, the MTZ should not be rechallenge, and if available, the prescription of a benzodiazepine may reduce recovery time.

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Rheumatoid arthritis (RA) is a common systemic autoimmune disease. Its major manifestation is persistent joint inflammation, which can lead to bone destruction and severe disability. The immunopathogenesis of RA is very complex, involving both innate and adaptive immune systems. Recently, the discovery of anti-citrullinated protein antibodies (ACPAs) has revolutionized the diagnosis and our understanding of the immunopathogenesis of RA. The presence of ACPAs is also closely linked to the disease activity of RA. Therefore, it is reasonable to believe that ACPAs and protein citrullination are key issues for the development of RA. We have summarized the recent study results in this review. The first theory concerning the pathogenesis of RA proposed that ACPAs link the well-known genetic and environmental risk factors for developing RA. However, due to the close association between joint inflammation and ACPAs, a more direct role of ACPAs in the immunopathogenesis of RA is anticipated. Within the past 10 years, many studies, including some of our own, have shown that ACPAs can promote an inflammatory response through complement activation, formation of neutrophil extracellular traps, and direct binding to key players, including monocytes, osteoclasts, and osteoblasts, in the mediation of bone destruction in the joints of RA patients. We also present some new perspectives and issues that need to be further investigated.

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Scar endometriosis is uncommon and defined as the presence of ectopic endometrial glands in abdominal soft tissues after a gynecological operation. Malignant transformation has been reported but remains rare. Carcinogenesis occurs in ectopic endometrial tissue with repeated hormone stimulation during the menstrual cycle. We present a case of clear cell carcinoma directly arising from scar endometriosis after a cesarean section and review all 16 cases reported.

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Objective: Arthropod-borne viral diseases are a major burden on the health-care system worldwide. Only a few studies have reported on coinfection of dengue fever (DF) with the chikungunya virus in North India. We investigated the seroprevalence and significance of the clinicobiochemical profile of dengue and chikungunya coinfection. Besides this, the authors try to emphasize rationalize platelets transfusion. Material and Methods: The present study was conducted at the Heritage Institute of Medical Science, Varanasi, India, from July to December 2016. A total of 1800 suspected cases with acute viral febrile illness (age >18 years) were investigated to exclude other causes of acute febrile illnesses. Of these, 121 patients (6.72%) were diagnosed as seropositive for dengue and chikungunya mono or coinfection using IgM ELISA and were included in the study. Results: The male gender was predominant. The majority were in the 20–30-year age group with cases peaking in November. There were 102 (84.29%) cases of dengue, 6 (4.95%) cases of chikungunya, and 13 (10.74%) cases positive for coinfection. Fever was present in all cases. Headache followed by nausea/vomiting and generalized weakness were the most common symptoms in patients with DF while body aches and joint pain were most common in those with chikungunya fever. Deranged liver function and leukopenia were the most common complications in dengue. Conclusion: Joint-related symptoms (pain and restricted movements) were statistically significant in chikungunya monoinfection. Two patients with DF were died. There was no significant added severity of clinical features and blood investigations in patients with coinfection with dengue and chikungunya compared to those with monoinfections.

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Objective: The incidence of gastroesophageal reflux disease (GERD) is increasing, and the disease has a close association with dietary habits. This study aims to investigate the role of tea and coffee drinking in the development of GERD. Materials and Methods: This study prospectively enrolled individuals who underwent an upper gastrointestinal endoscopy during a health checkup. Each participant completed the reflux disease questionnaire (RDQ). Coffee or tea drinking was defined as drinking the beverage at least 4 days/week for 3 months. Heavy coffee or tea consumption was defined as drinking at least two cups every day. Results: A total of 1837 participants (970 men; age 51.57 ± 10.21 years), who had data on clinical characteristics and consumption of coffee and tea with or without additives such as milk or sugar were included for final analysis. Among them, 467 (25.4%) were diagnosed as having symptomatic GERD based on the RDQ score, and 427 (23.2%) had erosive esophagitis (EE) on endoscopy. Drinking coffee or tea was not associated with reflux symptoms or EE in univariate and multivariate analyses. In contrast, drinking coffee with milk was associated with reflux symptoms and drinking “tea and coffee” was associated with EE in univariate analysis. However, these associations became insignificant after multivariate analysis. Conclusion: Drinking coffee or tea and adding milk or sugar was not associated with reflux symptoms or EE.

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Oral potentially malignant disorders (OPMD) are oral mucosal disorders which have a high potential to turn into malignancy. A recent report suggests that 16%–62% of epithelial dysplasia cases of OPMD undergo malignant transformation, showing the need for early detection of malignancy in these disorders. Micro RNA (miRNA) plays an important role in cellular growth, differentiation, apoptosis, and immune response, and hence, deregulation of miRNA is considered a signature of oral carcinogenesis. A search was done using MeSH terms in the PubMed, ScienceDirect databases, hand search, and finally, six studies were included in this systematic review. A total of 167 patients with oral cancer, 78 with OPMDs, 147 healthy controls, and 20 disease controls were analyzed for the expression of salivary miRNAs. Quality assessment based on the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to obtain a risk of bias chart using Revman 5.3 software and it was proved that the study done by Zahran et al. in 2015 had a low risk of bias. The results of this study revealed upregulated miRNA 184 with an area under the curve (AUC) of 0.86 and miRNA 21 with an AUC of 0.73 and downregulated miRNA 145 with an AUC of 0.68, which proved that these miRNAs are significant in detecting early malignancy in OPMD and should be further analyzed in various populations. This systematic review explored the potential of expression of salivary miRNA in OPMD for future studies. This could pave the way to utilize saliva as a surrogate marker in diagnosing early malignant changes in OPMD.

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Apart from the result of multiple diseases as well as aging, arterial stiffness (AS) predicts cardiovascular disease (CVD), especially in patients with chronic kidney disease (CKD). Patients with CKD have high CVD prevalence, and an extraordinarily high risk for CVD might be related to nontraditional risk factors, including AS. The mechanism of AS development could be attributed to oxidative stress, inflammation, uremic milieu (e.g., uremic toxins), vascular calcification, and cumulative effects of traditional cardiovascular risk factors on arteries such as diabetes mellitus or hypertension. There were a variety of non-invasive techniques to measure AS. One of these techniques is carotid–femoral pulse wave velocity, which is the reference measurement of AS and is related to long-term CVD outcomes. AS progression has corresponding medical treatments with modest beneficial results. This review briefly discusses the risk factors, measurements, and treatments associated with AS.

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Objective: The present study investigated the therapeutic potential and underlying mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) on joint cartilage destruction induced by monosodium iodoacetate (MIA) in mice. Materials and Methods: HUCMSCs were tested for mesenchymal stem cell (MSC) characteristics including surface markers by flow cytometry and mesoderm differentiation (adipogenesis, osteogenesis, and chondrogenesis). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Western blot assay were used to evaluate MIA-induced chondrocyte apoptosis. In the in vivo study, 18 mice were divided into three groups (n = 6 each); normal saline (control), MIA-treated, and MIA-treated/HUCMSC-transplantation. Rota-Rods tests were used to evaluate MIA-induced cartilage destruction behaviors in mice. Histological changes in the mice cartilage were examined by immunohistochemistry. Results: HUCMSCs had an immunophenotype similar to bone marrow-derived MSCs and were able to differentiate into adipocytes, osteocytes, and chondrocytes. Conditioned medium of the HUCMSCs exhibited an anti-apoptotic effect and inhibited expression of caspase 3 in MIA-treated chondrocytes. HUCMSC transplantation assisted in recovery from movement impairment (from 30% on day 7 to 115% on day 14) and in regeneration and repair of cartilage damaged by MIA. (International Cartilage Repair Society score: 3.8 in the MIA group vs. 10.2 in the HUCMSC-treated group); HUCMSC transplantation ameliorated cartilage apoptosis through the caspase 3 pathway in MIA-induced cartilage destruction in mice. Conclusion: Taken together, these observations suggest that HUCMSC transplantation appears to be effective in protecting cartilage from MIA damage.

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Objective: Leptin is an adipocyte-derived hormone and has shown positive correlation with obesity and metabolic syndrome (MetS) in many studies. However, there are few studies investigating this relation in elderly people. Therefore, we aimed to investigate the correlation between the fasting serum leptin level and MetS among older Taiwanese. Materials and Methods: The fasting serum leptin level was obtained from 62 Taiwanese participants over 65 years old and was measured using a commercially available enzyme immunoassay kit. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Results: Thirty elderly participants (48.4%) had MetS. The serum leptin level was positively correlated with MetS (P < 0.001). Multivariate logistic regression analysis of the factors significantly associated with MetS showed that logarithmically transformed leptin (log-leptin, each increase 0.1 ng/mL log-leptin, odds ratio: 1.276, 95% confidence interval: 1.015–1.603,P= 0.037) was still an independent predictor of MetS in elderly persons. Univariable linear analysis showed that body weight (r = 0280,P= 0.028), body mass index (r = 0.417,P= 0.001), waist circumference (r = 0.419,P= 0.001), blood urea nitrogen (r = 0255,P= 0.046), log-insulin (r = 0436,P< 0.001), and logarithmically transformed homeostasis model assessment of insulin resistance (r = 0359,P= 0.004) positively correlated with fasting serum log-leptin levels. Multivariate forward stepwise linear regression analysis of the factors significantly associated with fasting serum log-leptin levels revealed that waist circumference (adjusted R² = 0.083,P= 0.002), statin use (adjusted R² = 0.058,P= 0.016), and female gender (adjusted R² = 0.041,P= 0.034) were independent predictors of fasting serum log-leptin levels among elderly participants. Conclusion: In elderly Taiwanese, the serum leptin level was positively correlated with MetS. Waist circumference, statin use, and female gender were independent predictors of the fasting serum leptin level in elderly participants.

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Recent studies have reported that ischemia/reperfusion (I/R) may act in the immune system where an exaggerated inflammatory response is initiated. With the activation of the immune system, damage-associated molecular patterns migrate and adhere to the I/R region, consequently inducing multiorgan injury. Emerging data indicate that upon I/R, stress-inducible proteins, including activating transcription factor 3 (ATF3), play essential roles in signaling during antiapoptotic, antimigration, and anti-inflammatory processes. Accumulating data suggest that ATF3 may be a potential target in I/R- or inflammation-induced organ dysfunction. This minireview focuses on the emerging evidence of the roles of ATF3 in multiple organs including the kidney, myocardium, and brain following I/R injury. In addition, this review addresses the role of ATF3 in chronic inflammation-induced pathophysiologies such as diabetes and atherosclerosis.

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