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ID PMID Title PublicationDate abstract
35585977 Attenuation of Excess TNF-α Release in Crohn's Disease by Silencing of iRHOMs 1/2 and the 2022 TNFα converting enzyme (TACE) is a transmembrane metalloprotease that sheds an assortment of signaling receptors, cytokines, growth factors, and pro-inflammatory mediators. In Crohn's disease (CD), TACE activity is upregulated, resulting in a marked increase of TNFα secretion and inflammation. Although treatment of CD with TNFα monoclonal antibodies is beneficial, many patients are at risk for acquiring opportunistic infections, and the treatment efficacy of TNFα monoclonal antibodies typically decreases over time. This study investigated an alternative approach for mitigating TNFα release by knocking down TACE membrane translocation in macrophages via inhibitory rhomboid proteins 1 and 2 (iRHOMs 1/2) siRNA treatment. First we measured TGFβRII shedding in ex vivo plasma samples collected from CD patients and healthy control subjects (N=40 per group). Then, we measured TGFβRII shedding and the expression and production of TGFβ ligand, TNFα, IL-6, IL-1β, IL-10, and total versus membranous TACE in vitro with THP-1 derived macrophage infected with Mycobacterium avium subspecies paratuberculosis (MAP), a highly studied CD-related pathogen. We determined that TGFβRII shedding was significantly higher in CD patients compared to healthy controls [515.52 ± 54.23 pg/mL vs 310.81 ± 43.16 pg/mL, respectively], and MAP-infected CD plasma samples had significantly more TGFβRII shedding (601.83 ± 49.56 pg/mL) than MAP-negative CD samples (430.37 ± 45.73 pg/mL). Moreover, we also determined that TACE production; TGFβ ligand expression and production; and TGFβRII shedding were also higher in MAP-infected THP-1 macrophages. Nevertheless, once we transfected the MAP infected macrophages with iRHOM siRNA, TACE production and membrane localization were significantly decreased, resulting in a significant decrease in TGFβRII shedding; an increase in Smad3 phosphorylation; a decrease in the expression and production of pro-inflammatory cytokines; and a decrease in the expression and production of stricture-associated factor, plasminogen activator inhibitor-1 (PAI-1). Our data clearly demonstrates that the regression of TACE trafficking, via iRHOM 1/2 silencing, significantly reduces the release of TNFα and restores the immunosuppressive capabilities of TGFβ signaling, which ultimately reverses inflammatory tissue damage. Accordingly, this study may provide a framework for the creation of newer, safer therapeutic options designed to treat inflammatory autoimmune diseases such as CD and rheumatoid arthritis.
35360229 A Useful Blood Flow Restriction Training Risk Stratification for Exercise and Rehabilitati 2022 Blood flow restriction training (BFRT) is a modality with growing interest in the last decade and has been recognized as a critical tool in rehabilitation medicine, athletic and clinical populations. Besides its potential for positive benefits, BFRT has the capability to induce adverse responses. BFRT may evoke increased blood pressure, abnormal cardiovascular responses and impact vascular health. Furthermore, some important concerns with the use of BFRT exists for individuals with established cardiovascular disease (e.g., hypertension, diabetes mellitus, and chronic kidney disease patients). In addition, considering the potential risks of thrombosis promoted by BFRT in medically compromised populations, BFRT use warrants caution for patients that already display impaired blood coagulability, loss of antithrombotic mechanisms in the vessel wall, and stasis caused by immobility (e.g., COVID-19 patients, diabetes mellitus, hypertension, chronic kidney disease, cardiovascular disease, orthopedic post-surgery, anabolic steroid and ergogenic substance users, rheumatoid arthritis, and pregnant/postpartum women). To avoid untoward outcomes and ensure that BFRT is properly used, efficacy endpoints such as a questionnaire for risk stratification involving a review of the patient's medical history, signs, and symptoms indicative of underlying pathology is strongly advised. Here we present a model for BFRT pre-participation screening to theoretically reduce risk by excluding people with comorbidities or medically complex histories that could unnecessarily heighten intra- and/or post-exercise occurrence of adverse events. We propose this risk stratification tool as a framework to allow clinicians to use their knowledge, skills and expertise to assess and manage any risks related to the delivery of an appropriate BFRT exercise program. The questionnaires for risk stratification are adapted to guide clinicians for the referral, assessment, and suggestion of other modalities/approaches if/when necessary. Finally, the risk stratification might serve as a guideline for clinical protocols and future randomized controlled trial studies.
35146210 A case of Epstein-Barr virus acute retinal necrosis successfully treated with foscarnet. 2022 Mar PURPOSE: Epstein-Barr virus (EBV) is a herpes virus known to cause infectious mononucleosis and several other human disorders. Ocular EBV infections that have been reported include uveitis, retinal vasculitis, and acute retinal necrosis (ARN). ARN is usually caused by herpes simplex virus (HSV) or varicella-zoster virus (VZV). ARN that is caused by EBV (EBV-ARN) is rarely seen, and only a few cases have been reported. The visual prognosis for EBV-ARN is poor, and no treatment strategy has been established. We report on a patient who was treated successfully for EBV-ARN. OBSERVATION: An 80-year-old female who had been treated with prednisolone at 5 mg/day and methotrexate at 2 mg/week for rheumatoid arthritis visited our hospital because of blurred vision in her left eye. Her left visual acuity was 20/50, and extensive white-yellowish retinal lesions at the temporal periphery with retinal hemorrhages were seen through vitreous haze. The DNA sequence of EBV, but not of HSV, VZV, or cytomegalovirus, was detected by a polymerase chain reaction (PCR) assay in the aqueous humor (4.2 × 10(6) copies/ml), with EBV also being positive in serum (3.5 × 10(2) copies/ml). The patient received 2 mg of intravitreal ganciclovir injections twice with a 3-day interval and intravenous infusion of acyclovir at 750 mg/day for 7 days; however, the retinal white lesions expanded rapidly, then dose of prednisolone was increased (40 mg/day) and vitrectomy was performed 10 days after the initial visit. After the surgery, the retinal lesion continued to enlarge. Vitreous samples showed high copies of EBV (1.2 × 10(8) copies/ml). Following treatment with intravenous foscarnet (4800 mg/day), which replaced the acyclovir application, the retinal white lesions gradually diminished, leaving retinal scars. To date, the patient has developed no retinal detachment and shows visual acuity over 6/60 in the left eye along with silicone oil. CONCLUSIONS: We experienced a case of EBV-ARN that was refractory to systemic acyclovir and topical ganciclovir but responded effectively to systemic foscarnet after vitrectomy. Although the clinical management remains challenging in this disease, foscarnet is considered to be one of the candidate drugs for EBV infections.
34147317 De Quervain Tenosynovitis: An Evaluation of the Epidemiology and Utility of Multiple Injec 2022 Mar PURPOSE: We hypothesized that repeat injections are associated with a decreased rate of success and that the success rate of injections correlates with patient comorbidities. METHODS: Using a commercially available insurance database, patients diagnosed with De Quervain tenosynovitis were identified using International Classification of Diseases, Ninth Revision and Tenth Revision codes and stratified by therapeutic interventions, including therapy, injections, and surgery, as well as comorbidities. Injection failure was defined as a patient receiving a repeat injection or subsequent surgical management. Success was defined as no further therapies identified after an intervention. RESULTS: From 2007 to 2017, 33,420 patients with a primary diagnosis of De Quervain tenosynovitis were identified. Women represented 77.5% (25,908) of the total and were 2.6 times more likely to be diagnosed than men. Black patients were more likely to be diagnosed than White patients. Black and White women were found to have the highest incidence (relative risk 3.4 and 2.3, respectively, compared with White men). Age was also significantly correlated with an increased risk of diagnosis of the condition, with a peak incidence at the age of 40-59 years (relative risk, 10.6). Diabetes, rheumatoid arthritis, lupus, and hypothyroidism were associated with an increased risk of diagnosis. Overall, 53.3% of the patients were treated with injections, 11.6% underwent surgery, and 5.2% underwent therapy. Treatment with a single injection was successful in 71.9% of the patients, with 19.7% receiving a repeat injection and 8.4% treated with surgery. The overall success rate of subsequent injections was 66.3% for the second injection and 60.5% for the third. The initial injection had a higher rate of success in diabetics than in nondiabetics; however, the difference (2%) was not clinically relevant. CONCLUSIONS: Although the success rate for the treatment of De Quervains tenosynovitis decreases with multiple injections, repeat injections have a high rate of success and are a viable clinical option. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.
35354411 Pharmacokinetics and pharmacodynamics of a proposed tocilizumab biosimilar MSB11456 versus 2022 May BACKGROUND: Tocilizumab is a recombinant humanized monoclonal immunoglobulin G1 antibody against the interleukin-6 receptor (IL-6 R). MSB11456 is a proposed tocilizumab biosimilar. OBJECTIVES: To assess the pharmacokinetic and pharmacodynamic similarity of MSB11456 to both US-licensed and EU-approved tocilizumab. METHODS: Healthy adult volunteers (N = 685) received a single 162 mg subcutaneous injection of MSB11456, US-licensed tocilizumab, or EU-approved tocilizumab in this randomized, double-blind, parallel-group study. Blood samples were taken pre-dose and for up to 48 days post-dose. Primary endpoint pharmacokinetic parameters were analyzed using analysis of covariance. Secondary pharmacodynamic measures included serum-soluble IL-6 R and serum C-reactive protein. Safety data were analyzed descriptively. RESULTS: Pharmacokinetic equivalence (with all corresponding 90% confidence intervals for the geometric least squares mean ratios within the predefined 80.00% to 125.00% equivalence margin) was demonstrated between MSB11456 and both US-licensed and EU-approved tocilizumab, as well as between the reference products. Pharmacodynamic analyses demonstrated similarity of MSB11456 and both US-licensed and EU-approved tocilizumab, as well as between the reference products. Safety, tolerability, and immunogenicity were comparable between treatments. CONCLUSION: Pharmacokinetic and pharmacodynamic similarity of MSB11456, US-licensed tocilizumab, and EU-approved tocilizumab were demonstrated, and the three products had comparable immunogenicity and safety, supporting MSB11456 as a biosimilar to tocilizumab.
35580186 Focused ultrasound excites action potentials in mammalian peripheral neurons in part throu 2022 May 24 SignificanceModulation of peripheral nervous system (PNS) activity has shown promise in treating a wide range of diseases, from epilepsy to rheumatoid arthritis. Clinically, stimulation of nerves is most commonly delivered through invasive and risk-laden surgical electrode placement. Noninvasive technologies for PNS modulation can both increase safety and expand modulation application to various disease stages. Recent studies have revealed the therapeutic potential of noninvasive neuromodulation of brain circuits with ultrasound. This study identifies reliable protocols and molecular mechanisms for stimulating action potentials from individual peripheral neurons in the mammalian nervous system. These findings reveal the translational potential of ultrasound to effectively modulate the PNS through intrinsic neuronal mechanisms.
35458573 Evaluation of Molecular Test for the Discrimination of "Naked" DNA from Infectious Parvovi 2022 Apr 18 Low levels of parvovirus B19 (B19V) DNA can be detected in the circulation and in different tissue of immunocompetent individuals for months or years, which has been linked to inflammatory diseases such as cardiomyopathy, rheumatoid arthritis, hepatitis, and vasculitis. However, the detection of B19V DNA does not necessarily imply that infectious virions are present. This study aimed to evaluate the method based on the Benzonase(®) treatment for differentiation between the infectious virions from "naked" DNA in serum and bone marrow (BM) samples to be useful for the B19V routine diagnosis. In addition, we estimated the period of viremia and DNAemia in the sera and bone marrow of nonhuman primates experimentally infected with B19V. Serum samples from ten patients and from four cynomolgus monkeys experimentally infected with B19V followed up for 60 days were used. Most of the human serum samples became negative after pretreatment; however, only decreased viral DNA loads were observed in four patients, indicating that these samples still contained the infectious virus. Reduced B19V DNA levels were observed in animals since 7th dpi. At approximately 45th dpi, B19V DNA levels were below 10(5) IU/mL after Benzonase(®) pretreatment, which was not a consequence of active B19V replication. The test based on Benzonase(®) pretreatment enabled the discrimination of "naked DNA" from B19V DNA encapsidated in virions. Therefore, this test can be used to clarify the role of B19V as an etiological agent associated with atypical clinical manifestations.
35355711 Spectrum-Effect Relationship Analysis of Bioactive Compounds in Zanthoxylum nitidum (Roxb. 2022 Zanthoxylum nitidum (Roxb.) DC. (ZN), with strong effects of anti-inflammation and antioxidant activities is treated as a core herb in traditional Chinese medicine (TCM) preparation for treating stomachache, toothache, and rheumatoid arthritis. However, the active ingredients of ZN are not fully clarified due to its chemical complexity. In the present study, a double spectrum-effect analysis strategy was developed and applied to explore the bioactive components in herbs, and ZN was used as an example. Here, the chemical components in ZN were rapidly and comprehensively profiled based on the mass defect filtering-based structure classification (MDFSC) and diagnostic fragment-ion-based extension approaches. Furthermore, the fingerprints of 20 batches of ZN samples were analyzed by high-performance liquid chromatography, and the anti-inflammatory and antioxidant activities of the 20 batches of ZN samples were studied. Finally, the partial least squares regression (PLSR), gray relational analysis models, and Spearman's rank correlation coefficient (SRCC) were applied to discover the bioactive compounds in ZN. As a result, a total of 48 compounds were identified or tentatively characterized in ZN, including 35 alkaloids, seven coumarins, three phenolic acids, two flavonoids, and one lignan. The results achieved by three prediction models indicated that peaks 4, 12, and 17 were the potential anti-inflammatory compounds in ZN, whereas peaks 3, 5, 7, 12, and 13 were involved in the antioxidant activity. Among them, peaks 4, 5, 7, and 12 were identified as nitidine, chelerythrine, hesperidin, and oxynitidine by comparison with the standards and other references. The data in the current study achieved by double spectrum-effect analysis strategy had great importance to improve the quality standardization of ZN, and the method might be an efficiency tool for the discovery of active components in a complex system, such as TCMs.
35276223 Adalimumab with methotrexate versus adalimumab monotherapy in psoriasis: First-year result 2022 Mar 8 INTRODUCTION: Adalimumab is normally prescribed with methotrexate (MTX) in rheumatoid arthritis given the enhanced treatment effect and reduced antidrug antibody (ADA) formation compared to adalimumab monotherapy. In psoriasis, the long-term treatment effects and pharmacokinetic profile have not been investigated extensively. METHODS: We conducted a randomized controlled trial to assess the efficacy, safety, pharmacokinetics and immunogenicity of adalimumab combined with MTX (ADL-MTX group) compared to adalimumab monotherapy (ADL group) in chronic plaque psoriasis. RESULTS: Thirty-one patients in the ADL-MTX group and 30 in the ADL group were analysed.After one year, a (non-significant) better drug survival was found in the ADL-MTX group (74.2% vs 58.6%; p=0.15). The Psoriasis Area and Severity Index (PASI)75 response in week 49 was 58.1% vs. 36.7% (p=0.13) and the median (IQR) serum trough concentrations were 6.8 (5.5-9.2) vs. 5.9 (3.5-8.8)mg/L (p=0.26) in the ADL-MTX and ADL group respectively. Fewer patients showed ADA in the ADL group (22.6% vs. 60.0%; p<0.01). No serious adverse events (SAEs) occurred. CONCLUSION: Combination therapy of adalimumab and MTX results in less patients showing ADA, with a trend towards a better PASI75 response, drug survival and higher serum trough concentrations compared to adalimumab monotherapy. Patient reported outcomes and adverse events were comparable between the groups.
35153741 An Integrative Network Approach to Identify Common Genes for the Therapeutics in Tuberculo 2021 Tuberculosis (TB) is the leading cause of death from a single infectious agent. The estimated total global TB deaths in 2019 were 1.4 million. The decline in TB incidence rate is very slow, while the burden of noncommunicable diseases (NCDs) is exponentially increasing in low- and middle-income countries, where the prevention and treatment of TB disease remains a great burden, and there is enough empirical evidence (scientific evidence) to justify a greater research emphasis on the syndemic interaction between TB and NCDs. The current study was proposed to build a disease-gene network based on overlapping TB with NCDs (overlapping means genes involved in TB and other/s NCDs), such as Parkinson's disease, cardiovascular disease, diabetes mellitus, rheumatoid arthritis, and lung cancer. We compared the TB-associated genes with genes of its overlapping NCDs to determine the gene-disease relationship. Next, we constructed the gene interaction network of disease-genes by integrating curated and experimentally validated interactions in humans and find the 13 highly clustered modules in the network, which contains a total of 86 hub genes that are commonly associated with TB and its overlapping NCDs, which are largely involved in the Inflammatory response, cellular response to cytokine stimulus, response to cytokine, cytokine-mediated signaling pathway, defense response, response to stress and immune system process. Moreover, the identified hub genes and their respective drugs were exploited to build a bipartite network that assists in deciphering the drug-target interaction, highlighting the influential roles of these drugs on apparently unrelated targets and pathways. Targeting these hub proteins by using drugs combination or drug repurposing approaches will improve the clinical conditions in comorbidity, enhance the potency of a few drugs, and give a synergistic effect with better outcomes. Thus, understanding the Mycobacterium tuberculosis (Mtb) infection and associated NCDs is a high priority to contain its short and long-term effects on human health. Our network-based analysis opens a new horizon for more personalized treatment, drug-repurposing opportunities, investigates new targets, multidrug treatment, and can uncover several side effects of unrelated drugs for TB and its overlapping NCDs.
35148484 Prevalence of sagittal molar and canine relationships, asymmetries and midline shift in re 2022 Feb 11 OBJECTIVE: To examine the prevalence of sagittal relationships, asymmetries and midline shift, and their associations with temporomandibular disorders (TMD) in the Northern Finland Birth Cohort 1966 (NFBC1966). MATERIALS AND METHODS: 1845 subjects participated in a clinical examination at the age of 46. Occlusal measurements were performed using 3D models. Symptoms of TMD were screened using validated questions, and signs and diagnoses of TMD were assessed using a modified protocol of the Diagnostic Criteria for TMD (DC/TMD) and questionnaires. Associations between variables of occlusion and TMD were evaluated with χ(2)-test and Fisher's exact test and using logistic regression analyses, adjusted for self-reported general health, mental health, bruxism, and rheumatoid arthritis. RESULTS: The most common sagittal relationships were Class I and normal canine relationship. Half-cusp Class II and post-normal canine relationship were more frequent in females, and Class III and pre-normal canine relationship in males. Deviations from normal cuspid or molar relationships showed a weak but statistically significant association with TMD, especially in females. Half-cusp Class II and Class II relationships were more frequent in relation to joint-related TMD signs and diagnoses while missing canines were associated with pain-related TMD diagnoses. CONCLUSIONS: The present study findings gave some indications that canine relationships are associated with pain-related TMD, whereas Angle II sagittal occlusal relations may associate with joint-related TMD. Occlusal characteristics should therefore be taken into account as one possible associating factor in subjects with TMD.
35056384 A Lower Level of Post-Vaccinal Antibody Titer against Influenza Virus A H1N1 May Protect P 2022 Jan 4 Background and Objectives: The concentration of antibodies against virus influenza A H1N1 in the titer (≥1:32) positively correlates with resistance to flu in healthy persons. In elderly and immune-compromised patients, an influenza vaccine may be less immunogenic. Hypothesis: A lower post-vaccinal antibody titer (≥1:16) may be sero-protective against respiratory viral infections in patients with autoimmune rheumatic diseases. Materials and Methods: Fifty patients with autoimmune rheumatic diseases (Systemic Lupus Erythematosus-24; Rheumatoid Arthritis-15; and Sjögren's Syndrome-11), who were at least 65 years old or whose relative disease duration (disease duration/age) was greater than 1/8, were examined. Thirty-four of them were vaccinated with a trivalent inactivated non-adjuvant influenza vaccine. The antibody concentration against influenza virus A H1N1 was measured using the standardized hemagglutination inhibition test and patients who got any respiratory viral infection were registered. To test the hypothesis, a correlative analysis was applied, followed by a binary logistic regression that included potential confounding variables, such as age, disease duration and therapy (personal/health-related conditions). Results: Vaccinated patients were significantly less affected by respiratory viral infections (21% vs. 75%). The lower titer considered (≥1:16) was significantly present more often among vaccinated patients (68% vs. 6%). The correlation between its presence/absence and that of respiratory viral infections was -0.34 (p < 0.05). The binary logistic regression evidenced the relevance of this correlation, confirming the hypothesis. Vaccination was associated with the 87.3% reduction in the likelihood of getting respiratory viral infections, whereas the lower antibody titer (≥1:16) was associated with the 77.6% reduction in the likelihood of getting respiratory viral infections. The vaccine was well tolerated by all patients and after vaccination no exacerbation of the underlying disease was observed. Conclusions: A lower antibody titer (≥1:16) against influenza virus A H1N1 could be protective against respiratory viral infections for certain autoimmune rheumatic diseases patients, which confirms the clinical effectiveness of influenza vaccination.
34695593 Outcomes of radial head implants in total elbow arthroplasty. 2022 Mar BACKGROUND: There is no consensus on the management of the radial head in total elbow arthroplasty (TEA). In 3-part TEA designs, options include radial head retention, excision, or arthroplasty. Biomechanical studies suggest improved varus-valgus stability with radial head implants in unlinked total elbows. Unfortunately, complications with radial head implants have been common with historical designs. The aim of this study was to evaluate the clinical and radiographic outcomes of radial head implants in a current 3-part TEA and identify risk factors for mechanical failure. METHODS: We performed a retrospective review of radial head implants with a 3-part convertible TEA from 2001 to 2016. Clinical outcomes, functional scores, and radiographic outcomes were recorded. The preoperative radiocapitellar alignment was measured using the radiocapitellar ratio (RCR). Statistics include descriptive statistics, t tests, logistic regression, and Kaplan-Meier survival curves. RESULTS: We identified 44 TEAs in 40 patients, with a mean follow-up period of 7.2 years. The average age at surgery was 58 ± 11 years; 80% of the TEAs were performed in women. The indication for surgery was rheumatoid arthritis in 86%; of the implants, 61% were unlinked. The average preoperative RCR was 10.7 ± 17.9. Postoperatively, 2 radial head implants (5%) were subluxated, 6 (14%) were dissociated, and 2 (5%) were dissociated with implant dislocation on radiographic review. The revision rate for radial head subluxation, dissociation, or dislocation was 7% (n = 3). Univariate logistic regression showed that male sex (P = .002), abnormal preoperative RCR (P = .02), linked implant (P = .03), and older age (P = .04) were risk factors for radial head subluxation, dissociation, or implant dislocation. A multivariate model with all 4 variables did not demonstrate statistical significance. CONCLUSION: The incidence of radial head arthroplasty subluxation, dissociation, or implant dislocation was high (23%). In a univariate logistic regression model, male sex, abnormal preoperative RCR, and linked implants were all statistically significant risk factors for mechanical failure of the radial head implant. Our multivariate model did not show any statistically significant independent risk factors. Polyethylene wear or loosening of the radial head implants was not observed in this study; failure of the bipolar linkage was the principal mode of failure. Although further study is required, caution should be used when considering inserting a radial head implant in male patients with significant preoperative radiocapitellar malalignment. Radial head subluxation or dissociation is not an absolute indication for revision in an asymptomatic patient. Improvements in radial head implant designs in TEA are needed.
33783320 Emerging views of OPTN (optineurin) function in the autophagic process associated with dis 2022 Jan Macroautophagy/autophagy is a highly conserved process in eukaryotic cells. It plays a critical role in cellular homeostasis by delivering cytoplasmic cargos to lysosomes for selective degradation. OPTN (optineurin), a well-recognized autophagy receptor, has received considerable attention due to its multiple roles in the autophagic process. OPTN is associated with many human disorders that are closely related to autophagy, such as rheumatoid arthritis, osteoporosis, and nephropathy. Here, we review the function of OPTN as an autophagy receptor at different stages of autophagy, focusing on cargo recognition, autophagosome formation, autophagosome maturation, and lysosomal quality control. OPTN tends to be protective in most autophagy associated diseases, though the molecular mechanism of OPTN regulation in these diseases is not well understood. A comprehensive review of the function of OPTN in autophagy provides valuable insight into the pathogenesis of human diseases related to OPTN and facilitates the discovery of potential key regulators and novel therapeutic targets for disease intervention in patients with autophagic diseases.Abbreviations: ATG: autophagy-related; APAP: acetaminophen; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CC: coiled-coil; HACE1: HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1; MYO6: myosin VI; IKBKG/NEMO: inhibitor of nuclear factor kappa B kinase regulatory subunit gamma; IKK: IκB kinase; LIR: LC3-interacting region; LZ: leucine zipper; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NFKB/NF-κB: nuclear factor kappa B subunit; OPTN: optineurin; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RTECs: renal tubular epithelial cells; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; TOM1: target of myb1 membrane trafficking protein; UBD: ubiquitin-binding domain; ULK1: unc-51 like autophagy activating kinase 1; WIPI2: WD repeat domain, phosphoinositide interacting 2; ZF: zinc finger.
35561089 Compounds with NO Inhibitory Effect from the Rattan Stems of Sinomenium acutum, a Kind of 2022 May 13 Three new alkaloids (1-3), one new diphenyl ether (4) and fifteen known alkaloids (5-19) were isolated from the rattan stems of Sinomenium acutum. Comprehensive analyses of HR-ESI-MS, 1D ((1) H and (13) C), 2D-NMR ((1) H-(1) H COSY, HSQC, HMBC, NOESY), circular dichroism (CD), UV and IR revealed the structures and absolute configurations of these new compounds. The structures of other compounds were determined by comparison of their (1) H and (13) C-NMR data with previous literature reports. By measuring the amount of NO produced, the anti-inflammatory properties of the isolated compounds were studied. The results showed that compounds 4 and 5 had strong NO inhibitory activity.
35243795 Epidemiologic evaluation of pleurisy diagnosed by surgical pleural biopsy using data from 2022 Apr BACKGROUND: Pleural biopsies for investigating the causes of pleurisy are performed through modalities including needle biopsies, local anesthetic thoracoscopic procedures, and surgery (video-assisted thoracoscopic surgery and open thoracotomy). To date, there have been no large-scale nationwide epidemiological studies regarding pleurisy diagnosed via surgical pleural biopsy. This study examined the epidemiology of pleurisy diagnosed via surgical pleural biopsy in a Japanese nationwide administrative database. METHODS: We evaluated Japanese Diagnosis Procedure Combination data of 24 173 patients who underwent video-assisted thoracoscopic surgery or open thoracotomy and received a diagnosis of pleurisy between April 2014 and March 2020. In addition to pleurisy diagnoses, the patients' clinical information, including age, sex, smoking status (pack-years), dyspnea grade, length of in-hospital stay, and comorbidities, were extracted from the dataset. RESULTS: This study included data from 1699 patients. The most frequent causes of pleurisy were neoplastic diseases (55.9%; malignant mesothelioma 22.5%, lung cancer 15.7%, lymphoma 2.5%), followed by infectious diseases (24.0%; tuberculosis 16.2%, parapneumonic pleural effusion 3.6%, empyema 3.5%, nontuberculous mycobacteriosis 0.5%), collagen vascular diseases (2.8%; rheumatoid arthritis 1.3%, immunoglobulin G4-related diseases 0.7%, systemic lupus erythematosus 0.3%), and paragonimiasis (0.1%). CONCLUSIONS: Neoplastic diseases, including malignant mesothelioma and lung cancer, were frequently and accurately diagnosed as pleurisy via surgical pleural biopsy. The next leading cause was infectious diseases such as mycobacterial infections. Physicians should consider performing surgical biopsy in light of the knowledge regarding the etiology of pleurisy when a definitive diagnosis cannot be made via needle pleural biopsy.
34780984 A comprehensive review of research progress on the genus Arisaema: Botany, uses, phytochem 2022 Mar 1 ETHNOPHARMACOLOGICAL RELEVANCE: The genus Arisaema belongs to the family Araceae, which includes Chinese herbal medicines with wide-ranging pharmacological functions, including those useful for the treatment of stubborn phlegm, cough, epilepsy, tetanus, snakebite, rheumatoid arthritis, and other ailments. AIM OF THE STUDY: The current study aimed to comprehensively review the botany, uses, phytochemistry, pharmacology, toxicity, quality control and pharmacokinetics of plants in the genus Arisaema and to provide novel insights to develop future research in this field. MATERIALS AND METHODS: Relevant information on the genus Arisaema was obtained from published scientific materials (including materials from PubMed, Elsevier, Web of Science, Google Scholar, Baidu Scholar, CNKI, and Wiley) and other literature sources (e.g., the Chinese Pharmacopoeia, 2020 edition; Chinese herbal books and PhD and MSc thesis). RESULTS: The application information complied with this review and included processing techniques, traditional uses, clinical applications and classic prescriptions. Approximately 260 compounds, including flavonoids, alkaloids, saccharides, steroids, fatty acids, amino acids and volatile oils, have been separated and identified from the genus Arisaema. The isolated compounds exhibit wide-ranging pharmacological activities such as antitumor activity, analgesic and sedative activity, antioxidant activity and anti-inflammatory activity. The toxicity and irritant impacts, quality control, and pharmacokinetics are also discussed in this review. CONCLUSIONS: Plants in the genus Arisaema are valuable resources with therapeutic potential for a broad spectrum of ailments. Based on the limited literature, this review comprehensively and systematically summarizes current knowledge regarding the genus Arisaema for the first time. However, there have been insufficient studies on the active ingredients and germplasm and insufficient in-depth mechanistic studies. Therefore, isolation and identification of additional effective components and through research on the germplasm, pharmacodynamic mechanisms, and toxicology should be conducted to assess effectiveness and safety and to ensure the quality of the related drugs.
35469504 Combining individual patient data from randomized and non-randomized studies to predict re 2022 Apr 26 Meta-analysis of randomized controlled trials is generally considered the most reliable source of estimates of relative treatment effects. However, in the last few years, there has been interest in using non-randomized studies to complement evidence from randomized controlled trials. Several meta-analytical models have been proposed to this end. Such models mainly focussed on estimating the average relative effects of interventions. In real-life clinical practice, when deciding on how to treat a patient, it might be of great interest to have personalized predictions of absolute outcomes under several available treatment options. This paper describes a general framework for developing models that combine individual patient data from randomized controlled trials and non-randomized study when aiming to predict outcomes for a set of competing medical interventions applied in real-world clinical settings. We also discuss methods for measuring the models' performance to identify the optimal model to use in each setting. We focus on the case of continuous outcomes and illustrate our methods using a data set from rheumatoid arthritis, comprising patient-level data from three randomized controlled trials and two registries from Switzerland and Britain.
35380401 Aurothiomalate-Based Drugs as Potentially Novel Agents Against Leishmania major: A Mini Re 2022 Jun PURPOSE: Leishmaniasis is a major public health problem worldwide in many parts of the world. Current anti-leishmanial drugs have only limited clinical efficacy. Aurothiomalate derivatives are useful for treating rheumatoid arthritis, but have emerged as a promising therapeutic candidate for leishmaniasis. This paper gives a review of the literature about the usefulness of aurothiomalate derivatives against leishmaniasis. METHODS: In this study, we reviewed the proposed mechanisms of action of aurothiomalate and related compounds on the metabolism of L. major and collected data by searching relevant articles. RESULTS: Aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms: first, cytotoxic effects on parasites via thiomalate's false substrate role in the citric acid cycle against malate; and second, immunosuppressive and anti-inflammatory effects of aurothiomalate derivatives with prostaglandin production inhibitory effects. CONCLUSIONS: The current study documented that aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms of action. Gold thiomalate as a promising hit should be evaluated against L. major in vitro and in vivo conditions in the future.
35135447 Amelioration of Cisplatin-induced Renal Inflammation by Recombinant Human Golimumab in Mic 2022 BACKGROUND: One of the most commonly used anti-cancer agents, Cisplatin (CDDP) often causes nephrotoxicity by eliciting inflammation and oxidative stress. Golimumab, an anti-TNF biologic, is prescribed for the management of numerous inflammatory ailments like psoriatic and rheumatoid arthritis, ulcerative colitis and ankylosing spondylitis. OBJECTIVE: Current study has explored the effects of anti-TNF biologics golimumab on mice due to cisplatin-induced nephrotoxicity. METHOD: Renal toxicity was caused by administration of single cisplatin injection at 22 mg/kg by intraperitoneal (i/p) route. Golimumab (24 mg/kg, s.c.) was administered consecutively for 7 days. The parameters such as renal functions, oxidative stress, inflammation, and renal damage were evaluated on the 7th day of experiments. RESULTS: Cisplatin administration caused nephrotoxicity as shown by a significant elevation of various parameters viz; serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), urea nitrogen (BUN), and cystatin C. There was a significant rise in urinary clusterin, kidney injury molecule 1 (KIM-1), and β-N-acetylglucosaminidase (NAG) concentrations in the animals treated with cisplatin. The markers of oxidative stress (malondialdehyde, reduced glutathione, and catalase), inflammation (IL-6, TNF-α, IL-10, IL-1β, MCP-1, ICAM-1, and TGF-β1), and apoptosis (caspase-3) were also altered in serum and/or kidneys of cisplatin animals. Further, cisplatin-caused histopathological changes in proximal tubular cells as observed in the H&E staining of renal tissue. Golimumab treatment reduced all markers of kidney injury and attenuated cell death. Golimumab significantly reduced inflammatory cytokines TNFα, IL- 6, MCP-1, IL- 1β, ICAM-1, and TGF-β1 and increased anti-inflammatory cytokine IL-10 in cisplatin-intoxicated mice. CONCLUSION: The study's results suggest that golimumab prevented nephrotoxicity induced by cisplatin- through inhibition of oxidative stress, apoptotic cell death inflammatory response, thus improving renal function.