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ID PMID Title PublicationDate abstract
33519809 Vagus Nerve Stimulation Decreases Pancreatitis Severity in Mice. 2020 BACKGROUND: Vagus nerve stimulation (VNS) is effective in reducing inflammation in various diseases, such as rheumatoid arthritis, colitis and acute kidney injury. The anti-inflammatory effect of vagus nerve in these diseases necessitates the interactions of neural activation and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. In this study, we aimed to investigate the effect of VNS on severity in experimental acute pancreatitis (AP). METHODS: Two independent AP models were used, which induced in ICR mice with caerulein or pancreatic duct ligation (PDL). Thirty minutes after modeling, the left cervical carotid sheath containing the vagus nerve was electrically stimulated for 2 min. Plasma lipase and amylase activities, TNF-α levels and pancreas histologic damage were evaluated. In caerulein mice, the percentages of α7nAChR(+) macrophage in pancreas and spleen were assessed by flow cytometry. Furthermore, splenectomy and adoptive transfer of VNS-conditioned α7nAChR splenocytes were performed in caerulein mice to evaluate the role of spleen in the protective effect of VNS. RESULTS: VNS reduced plasma lipase and amylase activities, blunted the concentrations of TNF-α and protected against pancreas histologic damage in two AP models. Survival rates were improved in the PDL model after VNS. In caerulein AP mice, VNS increased the percentages of α7nAChR(+) macrophages in pancreas and spleen. Adoptive transfer of VNS-treated α7nAChR splenocytes provided protection against pancreatitis in recipient mice. However, splenectomy did not abolish the protective effect of VNS. CONCLUSIONS: VNS reduces disease severity and attenuates inflammation in AP mice. This effect is independent of spleen and is probably related to α7nAChR on macrophage.
33415907 Painful Sleep: Insomnia in Patients with Chronic Pain Syndrome and its Consequences. 2020 Dec 31 Insomnia is a chronic condition that occurs a minimum of three times per week over a period of three or more subsequent months. There are multiple causes of insomnia, and even though it is considered a symptom, it can be associated with chronic illnesses. Chronic pain syndrome, which is defined as pain that persists for a period longer than 3 months, is one of several etiologies of insomnia. The prevalence of insomnia among chronic pain patients is greater in comparison with the general population (percentage or ratio). Chronic pain is common in patients with rheumatoid arthritis, spinal pain (such as chronic back pain) and fibromyalgia. The prevalence of in-somnia is also higher in cancer patients when compared to the general population. When the clinical history indicates a straightforward diagnosis of chronic pain syndrome, patients will complain of insomnia as part of their symptomatology. It is imperative to manage their underlying illness to alleviate their sleep disorder. Various medications may be used to relieve and even improve pain symptoms. Other than pharmacological interventions, non-pharmacological alternatives such as yoga, meditation, acupuncture, and psychotherapy can help improve the quality of life of these patients. The purpose of this article is to review the diagnosis and management of insomnia in chronic pain syndrome and its impact on the quality of life.
33352101 Rheumatological Diseases in Denim Sandblasters with Silicosis: What Should Pulmonologists 2020 Nov OBJECTIVE: Silica exposure is not only the cause of silicosis, also associated rheumatological diseases like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). This report will reveal the rheumatological diseases of silicosis patients who were exposed to silica while working as denim sandblasters. Additionally, we will describe some clinical and laboratory findings that will help pulmonologist suspect, recognize and manage rheumatological diseases related to silica exposure in patients with silicosis. MATERIAL AND METHODS: We reviewed the records of 142 sandblasters diagnosed with silicosis and found ten silicosis cases who also had rheumatological diseases between the years 2009 and 2017. The occupational characteristics, serological, functional and radiological data, were collected for patients of silicosis with rheumatological diseases. RESULTS: Ten silicosis patients with concomitant rheumatological diseases were found. Six patients among our cases had diagnosed SSc (4.2%), three of them had RA (2.1%), and one of them was being monitored for SLE (0.7%). The mean silica exposure time of the cases was 4.3±1.9 years (min: 1 max: 8). We also found elevated LD, sedimentation and CRP levels in our cases. CONCLUSION: It should be kept in mind that, in silicosis cases with arthralgia, joint tenderness or sclerosis at the fingertips may be indicative of rheumatological diseases related to silica exposure, and in these cases, the unexplained elevations of sedimentation and CRP levels may also be a result of silica-induced rheumatological diseases.
33315186 Sjögren's Syndrome Associated With Thrombotic Thrombocytopenic Purpura: A Case-Based Revi 2021 Mar OBJECTIVE: To review all published cases of the rare association between thrombotic thrombocytopenic purpura (TTP) and Sjögren's syndrome (SS). The authors report an additional case of this unique association. METHODS: Systematic review of the literature and a case report. The database were articles published in PubMed/MEDLINE, Web of Science, LILACS, and SciELO, registered from 1966 to August 2020. The DESH terms were "Sjögren's syndrome" and "thrombotic thrombocytopenic purpura," without language limitation. RESULTS: Most patients were female (88%), and the age varied from 30 to 75 years old. Concerning the sequence of disease appearance, SS followed by TTP was seen in seven articles, TTP and SS in three, and simultaneous appearance of both diseases in three studies. Primary SS was observed in 16 patients, and secondary SS was detected in two cases: dermatomyositis and rheumatoid arthritis. Anemia was the most common TTP manifestation, followed by thrombocytopenia, fever, consciousness alteration, renal impairment, and schistocytes' appearance on a blood smear. Treatment involved plasmapheresis, plasma exchange, rituximab, glucocorticoid, and cyclophosphamide. A good outcome was noted in most studies; few patients died. CONCLUSIONS: TTP is a rare manifestation associated with SS. After the TTP diagnosis, plasmapheresis and/or plasma exchange should be immediately implemented.
33269129 Naltrexone-Associated Non-ST-Elevated Myocardial Infarction. 2020 Oct 27 Medications for opioid use disorder (MOUD) and opioid agonist therapy (OAT) are the mainstays of treatment in opioid use disorder. Significant caution is encouraged upon initiation to reduce the precipitation of opioid withdrawal. Cardiac events in the setting of opioid withdrawal are rare and incompletely understood. A 46-year-old woman with a history of opioid-use disorder, hypertension, hyperlipidemia, diabetes, tobacco-use disorder, and rheumatoid arthritis presented with nausea, vomiting, and lightheadedness after taking naltrexone following buprenorphine. She was found to be hypertensive and tachycardic in the emergency department, with a troponin of 0.38 ng/mL (reference: 0.00-0.30 ng/mL) and an electrocardiogram (ECG) without ST or T-wave changes. She was admitted for a non-ST-elevation myocardial infarction (NSTEMI) and hypertensive emergency in the setting of opioid withdrawal. Her blood pressure was controlled, and she received full-dose aspirin and high intensity atorvastatin. Afterwards she was started on a modified OAT regimen of buprenorphine 8 mg daily. Her cardiac enzymes down-trended and her condition became stable after which she was discharged home. Cardiac events are an uncommon yet lethal occurrence in opioid withdrawal. The likely etiology of NSTEMI in our patient was demand ischemia induced by opioid withdrawal, augmented by her various other cardiac risk factors. Practitioners should be aware of these possible adverse events, especially in those with preexisting cardiac disease. Meticulous efforts should be made to instruct patients as to the proper dosing schedule when initiating opioid therapy, and when initiating MOUD/OAT in order to prevent poor outcomes.
33163329 Side Effects of Chloroquine and Hydroxychloroquine on Skeletal Muscle: a Narrative Review. 2020 PURPOSE OF REVIEW: Concerning adverse neuromuscular effects, there are quite a few reports about the incidence and prevalence of chloroquine (CQ) and hydroxychloroquine (HCQ) myopathy. Given the above, I decided to explore the relationships of these drugs with skeletal muscle in an attempt to clarify how they affect the muscle now and in the future, as millions of people are using CQ and HCQ. RECENT FINDINGS: The literature review identified 28 publications about CQ/HCQ myopathy, totaling 56 patients, from 1963 to 2020. A compilation of all patients was carried out by computing demographic features, clinical aspects, laboratory exams, and clinical evolution. All articles but two represented a large series about incidence and prevalence of the myopathy. Fifty-nine percent used QC, mean daily dose was 393 mg per day, and mean duration of treatment was 37 months. The predominant underlying diseases were rheumatoid arthritis (42.8%) and lupus erythematosus (26.8%). Respiratory distress was present in 12.5% in patients with proximal muscle weakness (87.2%). Dysphagia and cervical and axial weakness were observed in a smaller percentage. Creatine kinase was elevated in 60.7%, and EMG showed a myopathic pattern in 54%. Muscle biopsy showed a vacuolar pattern in 53.7%, and curvilinear bodies (CB) were the predominant ultrastructural finding (86.8%). After drug withdrawal, 85.4% of patients improved, and 12.7% died from other causes than myopathy. SUMMARY: CQ and HCQ myopathy has been known for a long time, but the incidence is low, being described only with long-term use. The use of these drugs for a short period has not been reported, although a prolonged elimination half-life of these drugs actually exists.
33059412 Revisiting bronchoscopic intratumoral chemotherapy in malignant central airway obstruction 2020 Oct 15 Critical central airway obstruction has always been a dreaded complication to which interventional pulmonologist commonly encounters. There have been various modalities which are used for the management and palliation, which includes mechanical coring, laser, cryoextraction, electrocautery and airway stenting. Rigid bronchoscopy with or without jet ventilation has been corner stone of therapeutics and palliation of central airway obstruction. There are only a few conditions where it is not possible to use rigid bronchoscopy. Here we report a case of metastatic tracheal tumour which presented with critical airway obstruction in a patient who had atlantoaxial instability (AAI) due to rheumatoid arthritis. Here we used endobronchial ultrasound scope (EBUS) via esophageal route, i.e. EUS-B guided approach for sampling of the tracheal tumour, and intratumoral chemotherapy was instilled in multiple sessions, which resulted in shrinking of tumour, thus relieving the critical airway obstruction. This is the first report of using EUS-B approach for intratumoral chemotherapy for tracheal tumors. Bronchoscopic intratumoral chemotherapy therapy (BITC) in tracheal tumors is also one of the options but has not been explored much and there has been a dearth of literature for it.
33026206 Spondylodiscitis in hemodialysis patients: a new emerging disease? Data from an Italian Ce 2020 Oct 5 Hemodialysis (HD) patients are at high risk for infectious complications such as spondylodiscitis. The aim of this retrospective study was to evaluate the cases of infective spondylodiscitis occurred between May 2005 and October 2019 among HD patients at our center. In 14 years, there were 9 cases (mean age 69±12 years). The main comorbidities found were diabetes mellitus (55.6% of patients), hypertension (55.6%), bone diseases (22.2%), cancer (11.1%) and rheumatoid arthritis treated with steroids (11.1%). The clinical onset included back pain (100% of cases), fever (55.6%), neurological deficits (33.4%), leukocytosis (55.6%) and elevated CRP level (88.9%). Most cases were diagnosed by magnetic resonance imaging (66.7%) with more frequent involvement of lumbar region (77.8%). Blood cultures were positive in five patients (mostly for S. aureus); three of them used catheters as vascular access and, in two cases, their removal was necessary. The mean time interval between the onset of symptoms and the diagnosis was 34±42 days. All patients received antibiotic treatment for a mean duration of 6 weeks; most cases were initially treated with vancomycin or teicoplanin plus ciprofloxacin. Most patients (77.8%) recovered after a mean of 3.5 months; one patient had a relapse after 2 years and one patient had long-term neurologic sequelae. Infective spondylodiscitis in HD must be suspected in the presence of back pain, even in the absence of fever or traditional risk factors. An early diagnosis could improve the outcome. Close monitoring of vascular access, disinfection procedures and aseptic techniques are important to avoid this complication.
32964777 Prevalence of autoimmune disorders among bladder pain syndrome patients' relatives. 2021 Feb PURPOSE: Possible genetic background and autoimmune etiology of Bladder Pain Syndrome (BPS, formerly Interstitial Cystitis, IC) has been suggested. We studied whether familial clustering of BPS, other autoimmune diseases or fibromyalgia exist among BPS patients' genetically close relatives; possibly reflecting some common predisposing genetic background of these diseases. MATERIALS AND METHODS: Altogether 420 first- or second-degree relatives of 94 BPS patients fulfilling the NIDDK criteria were asked to fill in a survey on the self-reported diagnosis of urinary tract diseases, fibromyalgia and 23 autoimmune diseases, together with filling the O'Leary-Sant symptom score. The ones with high symptom scores were interviewed and, if necessary, referred to a further clinical consultation. The prevalence of other diseases was compared to previously published prevalence percentages. RESULTS: 334 (80%) of 420 family members returned the questionnaire. Only one of the relatives fulfilled the NIDDK criteria, and one sibling pair among the original BPS patients was found. Asthma, ulcerative colitis, fibromyalgia, iritis and rheumatoid arthritis were more common in the study population than in the reference populations. The reported prevalence of atopic dermatitis and rhinoconjunctivitis causing allergies were lower. In addition, the results show that the O'Leary-Sant symptom score is not reliable in screening for new BPS cases. CONCLUSIONS: Our study suggests that in BPS patients' families, fibromyalgia and autoimmune diseases including asthma, and especially the non-allergic form of asthma, may be over-represented.
32811217 Contraceptive practices in women with chronic medical conditions. 2021 May Contraception in women with severe medical conditions is a potential measure to reduce maternal mortality. We sought to determine the contraceptive use in women with medical conditions at the University Hospital of the West Indies (UHWI) in Jamaica to determine if there is room for improvement in contraceptive use. Participants were identified from the medical out-patient departments and questionnaires administered. Two hundred and sixty females between 18 and 44 years with varied chronic medical conditions were included. Those included were systemic lupus erythematosus (SLE), diabetes, hypertension (HTN), thyroid disease, cardiac and renal disease. The total current use of contraception was 58.4%, while 41.6% were not on contraceptives. The use of barrier methods and long-acting reversible contraceptives (LARCs) was 71% and 10%, respectively. The current use of contraception in patients with sickle cell disease (SCD) was 84% (p=.004) and in rheumatoid arthritis (RA), 14% (p=.028). Fifty-eight (58, 24.2%) of the women were using two or more methods of contraception. There is a role for improving contraceptive use among women with medical conditions as they are at increased risk of pregnancy complications.IMPACT STATEMENTWhat is already known on this subject? Women with medical comorbidities significantly contribute to both direct and indirect causes of maternal mortality. Contraception may play an integral role in reducing the risk of dying in chronically ill women; however, the use of contraception in this group is often suboptimal.What the results of this study add? This study adds to the literature that in this high-risk group, there is an underuse of long-acting reversible contraceptives, which is ideal for this population.What the implications are of these findings for clinical practice or further research? The results will provide evidence that this high-risk group of women should be targeted and counselled regarding their risk of morbidity and mortality in pregnancy as well as contraception use while their condition is optimised. From this evidence, services may be put in place in institutions, especially in low-resource settings.
32741026 Early estrogen-induced gene 1 facilitates osteoclast formation through the inhibition of i 2020 Sep Osteoclast-mediated inflammatory bone resorption is a major cause of many inflammatory bone disorders, including rheumatoid arthritis and periodontitis. However, the mechanisms regulating osteoclast differentiation in inflammatory settings are not well understood. We demonstrate here that early estrogen-induced gene 1 (EEIG1)-deficient mice are protected from inflammatory bone loss as determined with the use of models of lipopolysaccharide (LPS)-induced bone destruction. EEIG1-deficient macrophages markedly decreased RANKL- and TNFα-mediated osteoclastogenesis due to the downregulation of the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), which is an essential transcription factor for osteoclast formation. In contrast, expression of interferon regulatory factor 8 (IRF8), a transcriptional repressor that blocks osteoclast differentiation, is elevated in EEIG1-deficient macrophages relative to wild-type cells. We found that reduced expression of B lymphocyte-induced maturation protein-1 (Blimp1) by siRNA downregulated RANKL-induced EEIG1 levels, whereas overexpression of Blimp1 potentiated EEIG1 levels. Mechanistic studies revealed that EEIG1 forms a complex with Blimp1 to negatively regulate the expression of the anti-osteoclastogenic gene, Irf8. We elucidated a novel mechanism by which EEIG1 restricts IRF8 expression and function, thereby enhancing the osteoclast formation by contributing to Blimp1-mediated IRF8 regulation. Together, these findings identify EEIG1 as a key regulator of osteoclastogenesis and a possible therapeutic target for pathological bone destruction.
32700555 Hydroxychloroquine in COVID-19 Therapy: Protection Versus Proarrhythmia. 2020 Nov In recent months, the new coronavirus SARS-CoV-2 has emerged as a worldwide threat with about 4.2 million confirmed cases and almost 300 000 deaths. Its major clinical presentation is characterized by respiratory symptoms ranging from mild cough to serve pneumonia with fever and potentially even death. Until today, there is no known medication to improve clinical symptoms or even prevent or fight the infection. The search for a useful vaccination is ongoing and it will probably not be available before the end of 2020. In this review, we highlight hydroxychloroquine (HCQ) as a potential agent to prevent coronavirus disease 2019 (COVID-19) and reduce as well as shorten clinical symptoms. Moreover, it might serve as a potential post-exposition prophylaxis. Although it has been used in the treatment of rheumatoid arthritis, discoid or systemic lupus erythematosus, and malaria prophylaxis and therapy for decades, knowledge on HCQ as a potential treatment for COVID-19 is limited and multiple clinical trials have just emerged. Especially, rare HCQ side effects which were of minor importance for use in selected indications might gain major relevance with population-wide application. These rare side effects include retinopathy and-even more important-QT prolongation leading to sudden cardiac death by malignant arrhythmias.
32683662 The potential effect of Ramadan fasting on musculoskeletal diseases: new perspectives. 2021 Mar Ramadan, the ninth month of the Muslim lunar calendar, is a period of intermittent fasting alternated with moments of refeeding. The last decades have seen a growing number of reports that examine the potential effect of Ramadan intermittent fasting (RIF) on chronic musculoskeletal disorders. In this paper, we reviewed data that assessed the relationship of intermittent diurnal fasting during Ramadan with rheumatic diseases. Currently, recent evidence indicates that RIF may attenuate the inflammatory state by suppressing pro-inflammatory cytokine expression and reducing the body fat and the circulating levels of leukocytes. Therefore, it may be a promising non-pharmacological approach for managing the course of rheumatic inflammatory diseases. Despite differences between studies in daily fasting duration and dietary norms, there appears to be a consensus that most of the patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) who fasted Ramadan experienced relief of their symptoms. Nevertheless, further clinical trials are required to assess the effect of RIF on other musculoskeletal and bone disorders. Additionally, we evaluated the impact of RIF on chronic medication intake. Even if a few studies on this issue are available, the primary outcomes indicate that RIF does not significantly impair either compliance or tolerance to chronic medications. These findings may give some reassurance to patients with a specific fear of drug intake during this month. Key Points • Intermittent diurnal fasting during Ramadan can modulate the inflammatory status through the down-regulation of metabolic syndrome, the reduction of pro-inflammatory cytokines, and the reduction of circulating levels of leukocytes • Ramadan intermittent fasting (RIF) can effectively improve the activity of rheumatic inflammatory diseases. • Although further studies are still required, there seems no harm for patients with gout to participate in RIF. • Primary outcomes indicate that RIF may be a promising non-pharmacological intervention for the management of patients with osteoarthritis and osteoporosis.
32382577 Sema4D Aggravated LPS-Induced Injury via Activation of the MAPK Signaling Pathway in ATDC5 2020 Osteoarthritis (OA) is the most common chronic degenerative joint disease, and it remains the main cause of chronic disability in elderly individuals. Sema4D (semaphorin 4D) is involved in the immune system and related to bone injury, osteoporosis, osteoblast differentiation, and rheumatoid arthritis. However, the role of Sema4D in OA remains unclear. Hence, the LPS-stimulated chondrocyte cell injury model was constructed in this study to investigate the role of Sema4D in OA development. The results showed that Sema4D was increased in LPS-treated ATDC5 cells, and the knockdown of Sema4D suppressed the decline of cell viability, the increase of cell apoptosis, and the increase of IL-6, IL-1β, and TNF-α secretion in ATDC5 cells induced by LPS. Meanwhile, Sema4D overexpression aggravated the cell injury triggered by LPS, and inhibiting Plexin B1 partly abolished the effect of Sema4D overexpression on LPS-induced chondrocyte injury. Furthermore, silencing of Sema4D blocked the activation of the MAPK pathway in LPS-stimulated ATDC5 cells. Enhanced Sema4D promoted the activation of the MAPK pathway in LPS-stimulated ATDC5 cells. What is more, inhibiting the MAPK signaling pathway abolished the promoting effect of Sema4D overexpression on LPS-induced chondrocyte injury. Therefore, our study suggested that the knockdown of Sema4D protects ATDC5 cells against LPS-induced injury through inactivation of the MAPK signaling pathway via interacting with Plexin B1.
32335517 Successful Mastectomy and Chemotherapy in a Patient with Breast Cancer and Active Generali 2020 Apr INTRODUCTION: Pyoderma gangrenosum (PG) is a rare, ulcerating neutrophilic dermatosis often associated with inflammatory bowel disease, rheumatoid arthritis, and myeloproliferative disorders. The classic description of PG includes irregularly shaped ulcers with undermined edges with a gun-metal gray or violaceous hue. The etiology remains unclear but appears to be related to genetically predisposed dysregulation of the innate immune system. Diagnosis of PG can be difficult as it can present with symptoms similar to cutaneous infections including erythema, edema, ulceration, fever and leukocytosis. Surgical procedures are generally contraindicated in patients with PG due to the risk of pathergy, excessive cutaneous injury, or ulceration in response to trauma. CASE REPORT: The authors report the development of PG with the initiation of chemotherapy in a 46-year-old woman with breast cancer. The patient had a complicated clinical course after multiple surgical debridements due to an initial misdiagnosis of necrotizing fasciitis. The patient's rapid onset of post-procedural ulceration was consistent with the pathergy of PG. The diagnosis of PG was confirmed by skin biopsy, which revealed a diffuse neutrophilic infiltrate, and with the patient's negative cultures and response to steroids. The patient was treated with perioperative prednisone and intravenous immunoglobulin prior to a mastectomy for her breast cancer. The surgery was not complicated by pathergy. CONCLUSIONS: This unique case highlights the challenging aspects in the medical and perioperative management of active PG in a patient with breast cancer.
32610074 Epigenetic and transcriptional regulation of osteoclastogenesis in the pathogenesis of ske 2020 Sep OBJECTIVES: To identify epigenetic and transcriptional factors controlling osteoclastogenesis (OCG), that have been shown to play a role in the pathogenesis of skeletal diseases. METHODS: A systematic review was conducted in accordance with the PRISMA guidelines. The PubMed and EMBASE databases were searched up to 30th April 2020; references of included articles and pertinent review articles were also screened to identify eligible studies. Studies were included if they described epigenetic and/or transcriptional regulation of OCG in a specific skeletal disorder, and quantified alterations in OCG by any well-described experimental method. Risk of bias was assessed by a previously described modification of the CAMARADES tool. RESULTS: The combined searches yielded 2265 records. Out of these, 24 studies investigating 12 different skeletal disorders were included in the review. Osteoporosis, followed by osteopetrosis, was the most commonly evaluated disorder. A total of 22 different epigenetic and transcriptional regulators of OCG were identified; key epigenetic regulators included DNA methylation, histone methylation, histone acetylation, miRNAs and lncRNAs. In majority of the disorders, dysregulated OCG was noted to occur at the stage of formation of committed osteoclast from preosteoclast. Dysregulation the stage of formation of the preosteoclast from late monocyte was noted in rheumatoid arthritis and fracture, whereas dysregulation at stage of formation of late monocyte from early monocyte was noted in osteopetrosis and spondyloarthritis. Quality assessment revealed a high risk of bias in domains pertaining to randomization, allocation concealment, blinding of outcome assessors and determination of sample size. CONCLUSIONS: A variety of epigenetic and transcriptional factors can result in dysregulated osteoclastogenesis in different skeletal disorders. Dysregulation can occur at any stage; however, the formation of committed osteoclasts from preosteoclasts is the most common target. Although the published literature on this subject seems promising, the overall strength of evidence is limited by the small number of studies evaluating individual skeletal disorders, and also by deficiencies in key aspects of study design.
32210615 Quercetin Inhibits Epithelial-to-Mesenchymal Transition (EMT) Process and Promotes Apoptos 2020 BACKGROUND: Prostate cancer (PC) is one of the most common carcinomas in men worldwide. The lack of effective therapies urges the development of novel therapeutic options against PC. Quercetin (Quer) is a flavonoid compound that has been shown to effectively inhibit PC in vitro and in vivo. However, the underlying mechanisms await elucidation. Long non-coding RNA MALAT1 has been reported as an oncogenic target in multiple types of cancers, including PC. Previous data showed that quercetin promoted the apoptosis of fibroblast-like synoviocytes by upregulating MALAT1 in rheumatoid arthritis. However, we speculate that mechanisms are different in PC. MATERIALS AND METHODS: Human PC cell line PC-3 and its xenograft tumor were chosen as in vitro and in vivo models for PC. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of MALAT1 in quercetin treatment against PC. Western blot was performed to measure the expression of related proteins to explore underlying molecular mechanisms. RESULTS: We showed for the first time that MALAT1 expression was significantly downregulated in quercetin-treated PC cells in a dose- and time-dependent manner. Also, quercetin inhibited the proliferation of PC cells and the growth of xenograft tumors. Moreover, quercetin suppressed EMT process, promoted apoptosis and deactivated PI3K/Akt signaling pathway during the progression of PC. MALAT1 overexpression in PC cells resulted in the resistance against quercetin treatment. CONCLUSION: Our study illustrated, for the first time, that MALAT1 played an important role in quercetin treatment against PC by inhibiting EMT process and promoting apoptosis, providing a new molecular basis for the application of quercetin in PC treatment.
32184036 Clinical significance of miRNAs in autoimmunity. 2020 May MicroRNAs (miRNAs) are evolutionally conserved, single-stranded RNAs that regulate gene expression at the posttranscriptional level by disrupting translation. MiRNAs are key players in variety of biological processes that regulate the differentiation, development and activation of immune cells in both innate and adaptive immunity. The disruption and dysfunction of miRNAs can perturb the immune response, stimulate the release of inflammatory cytokines and initiate the production of autoantibodies, and contribute to the pathogenesis of autoimmune diseases, including systemic lupus erythmatosus (SLE), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), and multiple sclerosis (MS). Accumulating studies demonstrate that miRNAs, which can be collected by noninvasive methods, have the potential to be developed as diagnostic and therapeutic biomarkers, the discovery and validation of which is essential for the improvement of disease diagnosis and clinical monitoring. Recently, with the development of detection tools, such as microarrays and NGS (Next Generation Sequencing), large amounts of miRNAs have been identified and suggest a critical role in the pathogenesis of autoimmune diseases. Several miRNAs associated diagnostic biomarkers have been developed and applied clinically, though the pharmaceutical industry is still facing challenges in commercialization and drug delivery. The development of miRNAs is less advanced for autoimmune diseases compared with cancer. However, drugs that target miRNAs have been introduced as candidates and adopted in clinical trials. This review comprehensively summarizes the differentially expressed miRNAs in several types of autoimmune diseases and discusses the role and the significance of miRNAs in clinical management. The study of miRNAs in autoimmunity promises to provide novel and broad diagnostic and therapeutic strategies for a clinical market that is still in its infancy.
32166424 Neonatal Organ and Tissue Donation for Research: Options Following Death by Natural Causes 2020 Jun The donation of organs and tissues from neonates (birth to 28 days) for transplantation has been a relatively infrequent occurrence. Less common has been the use of neonatal organs and tissues for research. Specific ethical and legal questions beg for rational and transparent guidelines with which to evaluate referrals of potential donors. Donation of organs and tissues from a neonate can play a key role in the care and support provided to families by health care professionals around the time of a neonate's death. We report on the recovery of neonatal organs and tissues for research. A working group made up of bioethicists, neonatologists, lawyers, obstetric practioners as well as organ procurement and tissue banking professionals evaluated legal, ethical and medical issues. Neonatal donor family members were also consulted. Our primary goals were (a) to ensure that referrals were made in compliance with all applicable federal and state laws, regulations and institutional protocols, and (b) to follow acceptable ethical standards. Algorithms and policies designed to assist in the evaluation of potential neonatal donors were developed. Neonatal donation is proving increasingly valuable for research into areas including diabetes, pulmonary, gastrointestinal, genitourinary and neurological development, rheumatoid arthritis, autism, childhood psychiatric and neurologic disorders, treatment of MRSA infection and pediatric emergency resuscitation. The development of policies and procedures will assist medical professionals who wish to offer the option of donation to family members anticipating the death of a neonate.
32117297 The Role of Mast Cells in Bone Metabolism and Bone Disorders. 2020 Mast cells (MCs) are important sensor and effector cells of the immune system that are involved in many physiological and pathological conditions. Increasing evidence suggests that they also play an important role in bone metabolism and bone disorders. MCs are located in the bone marrow and secrete a wide spectrum of mediators, which can be rapidly released upon activation of mature MCs following their differentiation in mucosal or connective tissues. Many of these mediators can exert osteocatabolic effects by promoting osteoclast formation [e.g., histamine, tumor necrosis factor (TNF), interleukin-6 (IL-6)] and/or by inhibiting osteoblast activity (e.g., IL-1, TNF). By contrast, MCs could potentially act in an osteoprotective manner by stimulating osteoblasts (e.g., transforming growth factor-β) or reducing osteoclastogenesis (e.g., IL-12, interferon-γ). Experimental studies investigating MC functions in physiological bone turnover using MC-deficient mouse lines give contradictory results, reporting delayed or increased bone turnover or no influence depending on the mouse model used. By contrast, the involvement of MCs in various pathological conditions affecting bone is evident. MCs may contribute to the pathogenesis of primary and secondary osteoporosis as well as inflammatory disorders, including rheumatoid arthritis and osteoarthritis, because increased numbers of MCs were found in patients suffering from these diseases. The clinical observations could be largely confirmed in experimental studies using MC-deficient mouse models, which also provide mechanistic insights. MCs also regulate bone healing after fracture by influencing the inflammatory response toward the fracture, vascularization, bone formation, and callus remodeling by osteoclasts. This review summarizes the current view and understanding of the role of MCs on bone in both physiological and pathological conditions.