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ID PMID Title PublicationDate abstract
34483390 Predictive Factors for Blood Transfusion after Total Knee Arthroplasty. 2021 Aug Objectives  The present paper aims to (1) verify the incidence and volume of blood transfusion among patients undergoing unilateral cemented total knee arthroplasty (TKA) in a single Brazilian reference center; (2) identify pre and perioperative variables to determine subjects with higher risk (i.e., predictive factors) for blood transfusion within 48 hours following surgery; (3) estimate the risk of blood transfusion during the first 48 hours after the procedure. Methods  The initial sample consisted of all patients undergoing TKA from August 2010 to August 2013. After applying the exclusion criteria, 234 patients aged 30 to 83 years old and diagnosed with primary or secondary osteoarthritis due to rheumatoid arthritis remained in the study. Results  Preoperative hemoglobin levels ≤ 12.3 g/dL and ischemia time ≥ 87 minutes were independent predictors for post-TKA blood transfusion, with a relative risk of 2.48 and 1.78, respectively. Approximately half of the TKA patients (51.3%) presenting these two variables required a blood transfusion. Conclusion  The incidence of post-TKA blood transfusion was 33.7%. On average, each transfused patient received 480 mL of packed red blood cells. Preoperative hemoglobin levels ≤ 12.3 g/dL ( p  < 0.001) and ischemia time ≥ 87 minutes ( p  < 0.047) were independent predictors for blood transfusion in TKA using a pneumatic cuff, with a relative risk of 2.48 and 1.78, respectively. Age, gender, diagnosis, or body mass index were not considered independent predictors for the need for blood transfusion up to 48 hours after the procedure.
32312711 Characterization of BAY 1905254, an Immune Checkpoint Inhibitor Targeting the Immunoglobul 2020 Jul The immunoglobulin-like domain containing receptor 2 (ILDR2), a type I transmembrane protein belonging to the B7 family of immunomodulatory receptors, has been described to induce an immunosuppressive effect on T-cell responses. Besides its expression in several nonlymphoid tissue types, we found that ILDR2 was also expressed in fibroblastic reticular cells (FRC) in the stromal part of the lymph node. These immunoregulatory cells were located in the T-cell zone and were essential for the recruitment of naïve T cells and activated dendritic cells to the lymph nodes. Previously, it has been shown that an ILDR2-Fc fusion protein exhibits immunomodulatory effects in several models of autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and type I diabetes. Herein, we report the generation and characterization of a human/mouse/monkey cross-reactive anti-ILDR2 hIgG2 antibody, BAY 1905254, developed to block the immunosuppressive activity of ILDR2 for cancer immunotherapy. BAY 1905254 was shown to promote T-cell activation in vitro and enhance antigen-specific T-cell proliferation and cytotoxicity in vivo in mice. BAY 1905254 also showed potent efficacy in various syngeneic mouse cancer models, and the efficacy was found to correlate with increasing mutational load in the cancer models used. Additive or even synergistic antitumor effects were observed when BAY 1905254 was administered in combination with anti-PD-L1, an immunogenic cell death-inducing chemotherapeutic, or with tumor antigen immunization. Taken together, our data showed that BAY 1905254 is a potential drug candidate for cancer immunotherapy, supporting its further evaluation.
32215271 Uncovering the Mechanism of Astragalus membranaceus in the Treatment of Diabetic Nephropat 2020 BACKGROUND: Diabetic nephropathy (DN), characterized by hyperglycemia, hypertension, proteinuria, and edema, is a unique microvascular complication of diabetes. Traditional Chinese medicine (TCM) Astragalus membranaceus (AM) has been widely used for DN in China while the pharmacological mechanisms are still unclear. This work is aimed at undertaking a network pharmacology analysis to reveal the mechanism of the effects of AM in DN. Materials and Methods. In this study, chemical constituents of AM were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential targets of AM were identified using the Therapeutic Target Database (TTD). DisGeNET and GeneCards databases were used to collect DN-related target genes. DN-AM common target protein interaction network was established by using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the DN mechanism and therapeutic effect of AM. The network diagrams of the active component-action target and protein-protein interaction (PPI) networks were constructed using Cytoscape software. RESULTS: A total of 16 active ingredients contained and 78 putative identified target genes were screened from AM, of which 42 overlapped with the targets of DN and were considered potential therapeutic targets. The analysis of the network results showed that the AM activity of component quercetin, formononetin, calycosin, 7-O-methylisomucronulatol, and quercetin have a good binding activity with top ten screened targets, such as VEGFA, TNF, IL-6, MAPK, CCL3, NOS3, PTGS2, IL-1β, JUN, and EGFR. GO and KEGG analyses revealed that these targets were associated with inflammatory response, angiogenesis, oxidative stress reaction, rheumatoid arthritis, and other biological process. CONCLUSIONS: This study demonstrated the multicomponent, multitarget, and multichannel characteristics of AM, which provided a novel approach for further research of the mechanism of AM in the treatment of DN.
35117543 A retrospective study on the clinical characteristics and radiological features of primary 2020 Mar BACKGROUND: The retrospective study was mainly performed to determine the clinical symptoms and radiological characteristics of primary pulmonary lymphoma (PPL) to improve the recognition and diagnosis of the disease. METHODS: Between June 2007 and June 2019, the clinical data and radiological images of the 16 patients with PPL confirmed by pathology were retrospectively analyzed. RESULTS: Among the 16 patients with PPL (6 males and 10 females, aged 32 to 72 years, with a median age of 55.13 years), 9 patients were mucosa-associated lymphoid tissue lymphoma (MALT) and 7 patients were diffuse large B-cell lymphoma (DLBCL); all of the patients did not suffer from autoimmune disease [such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or Sjogren's syndrome (SSS)]; and 11 patients had a long-term smoking history from 10 to 40 years. The common clinical symptoms were as follows: chest discomfort (n=8), cough (n=10), chest pain (n=7), fever (n=6), apnea (n=1), fatigue (n=4) and weight loss (n=3), however, 6 cases did not show clear symptoms at the time of diagnosis. Blood tests revealed anemia (n=6), thrombocytopenia (n=2), lactate dehydrogenase (LDH) level (n=7), C-reactive protein (CRP) (n=9), erythrocyte sedimentation rate (ESR) (n=8) and no tumor-related indexes were detected abnormal. The chest radiological images showed a total of 8 cases with multiple masses, 2 cases with different types of nodes, 4 cases with patchy infiltration or consolidation shadow, with or without an air bronchogram, and 2 cases with a mixed manifestation. All the lesions were only involved in unilateral lung (13 right, 3 left), none of them located on bilateral lung fields. At the time of admission, the patients were misdiagnosed as lung cancer (n=9), pneumonia (n=5), tuberculosis (n=1), and diffuse interstitial lung disease (n=1). Then final pathological diagnosis was confirmed by surgery (n=9), percutaneous lung biopsy (n=5), and bronchoscopic biopsy (n=2). CONCLUSIONS: PPL is a rare disease, though clinical symptoms and radiological characteristics are not typical, they serve as significant clues for the diagnosis and differential diagnosis. Accurate diagnosis mainly depends on histopathological examination, however, conducting a retrospectively study could improve and enrich our knowledge to the disease and reduce inappropriate treatments.
33297790 Preparation, characterization and in-Vitro/in-Vivo evaluation of meloxicam extruded pellet 2021 Jan OBJECTIVE: The present study involved enhancement of Meloxicam (MX) oral absorption for rapid onset of therapeutic action. A challenging approach using hot-melt-extrusion technique (HME) for production of stable novel preparation of MX pellets was successfully proposed. METHODS: Manipulating HME processing parameters (barrel-temperatures and screw-speed) and proper polymer(s) selection (Soluplus, a combination of Soluplus/Poloxamar and Polyethylene Glycol 6000) were the main strategies involved for productive extrusion of MX. Evaluation of MX solid-state (TGA, DSC and PLM), absolute percent crystallinity, in-vitro dissolution (in acidic/aqueous pHs), and stability testing in accelerated conditions up to 6-months as well as a long-term shelf for 36-months were performed. A comparative bioavailability study of selected MX-Pellets was carried-out against the innovator product (Mobic(®)) in 6 healthy volunteers under fed-conditions. RESULTS: TGA, DSC and PLM analyses proved the dispersion of MX in amorphous-state within polymeric matrix by HME. MX/Soluplus pellets exhibited the lowest crystallinity % and best dissolution performance among other polymers in both pHs. In addition, presence of Soluplus safeguards final pellets stability under different storage conditions. MX rate of absorption (T(max)) from Soluplus-based pellets attained a value of 45 min, which was 6-times faster than Mobic(®) (4.5 hr). CONCLUSION: A promising oral MX formula prepared by HME was successfully developed with a rapid onset of analgesic action (T(max) of 45 mins; almost 2-times faster than reported intramuscular injection), hence appropriate in the early relief of pain associated with rheumatoid arthritis and osteoarthritis. Moreover, the proposed formula was physico-chemically stable up to 36 months of shelf-life storage.
32956854 Incidence of and risk for osteonecrosis of the jaw in Korean osteoporosis patients treated 2021 Feb PURPOSE: To estimate the incidence of osteonecrosis of the jaw (ONJ) in patients treated with bisphosphonates (BPs) and to identify clinical risk factors that increase the risk for ONJ in Korean osteoporosis patients. METHODS: We used data acquired from the Korean National Health Insurance Service. Among 2,140,149 participants with osteoporosis in 2012, we selected 164,926 new BP users and 164,926 age- and sex-matched control subjects. The control group included only patients with no prescriptions for BPs between January 1, 2011, and December 31, 2016. Participants were followed for 4 years. RESULTS: Over the 4-year follow-up period, the cumulative incidence rates of ONJ were 20.9 and 6.9 per 100,000 person-years in the BP and control groups, respectively. The BP group had an increased risk for ONJ compared to the control group after adjusting for multiple variables (hazard ratio [HR] 3.72, 95% CI 2.70-5.11). Advanced age (≥70 years), comorbid diseases such as diabetes, hypertension, and rheumatoid arthritis (RA) were independent risk factors for the development of ONJ. In addition, tooth extraction (HR 9.85), gingivitis, and periodontal disease (HR 4.78) were strongly associated with ONJ. CONCLUSIONS: ONJ incidence was 21 per 100,000 person-years in osteoporosis patients receiving bisphosphonates. Clinical factors including advanced age, diabetes, RA, dental disease, as well as BP use were significantly associated with ONJ.
32592715 Statins and autoimmunity: State-of-the-art. 2020 Oct HMG-CoA reductase inhibitors, or statins, are potent plasma LDL-cholesterol (LDL-c) lowering agents. Since the introduction of the first statin, lovastatin, in 1987, accumulating evidence showed that non-cholesterol lowering effects play an important role in their efficacy to reduce atherosclerotic cardiovascular disease (ASCVD). Thus, these non-LDL-c lowering properties could benefit patients with immune-mediated diseases. Statins and their associated immune-modulating roles have recently received much attention. Different statins have been administered in various experimental and clinical studies focused on autoimmunity. The results indicate that statins can modulate immune responses through mevalonate pathway-dependent and -independent mechanisms. The anti-inflammatory and immune-modulating effects include cell adhesion, migration of antigen presenting cells, and differentiation, as well as activation, of T-cells. In various autoimmune diseases (e.g. rheumatoid arthritis, lupus, and multiple sclerosis), promising results have been obtained to date.
32527540 Discovery of triazolo [1,5-a] pyridine derivatives as novel JAK1/2 inhibitors. 2020 Jul 15 Small molecule JAK inhibitors have been demonstrated efficacy in rheumatoid arthritis, inflammatory bowel disease, and psoriasis with the approval of several drugs. Aiming to develop potent JAK1/2 inhibitors, two series of triazolo [1,5-a] pyridine derivatives were designed and synthesized by various strategies. The pharmacological results identified the optimized compounds J-4 and J-6, which exerted high potency against JAK1/2, and selectivity over JAK3 in enzyme assays. Furthermore, J-4 and J-6 effectively suppressed proliferation of JAK1/2 high-expression BaF3 cells accompanied with acceptable metabolic stability in liver microsomes. Therefore, J-4 and J-6 might serve as promising JAK1/2 inhibitors for further investigation.
32322594 Characterization of a Complex Mixture of Immunomodulator Peptides Obtained from Autologous 2020 A complex mixture of peptides plays a key role in the regulation of the immune system; different sources as raw materials mainly from animals and vegetables have been reported to provide these extracts. The batch-to-batch product consistency depends on in-process controls established. However, when an immunomodulator is a customized product obtained from the same volunteer who will receive the product to personalize the treatment, the criteria to establish the consistency between volunteers are different. In this sense, it is expected to have the same molecular weight range although the profile of peptide abundance is different. Here, we characterized the peptide profile of three extracts of an immunomodulator obtained from the urine of different volunteers suffering from three different diseases (i.e., allergic rhinitis, rheumatoid arthritis, and chronic rhinopharyngitis), using size exclusion chromatography (SEC) and mass spectrometry (MS). The peptides contained in the immunomodulators were stable after six months, stored in a refrigerator. Our results showed a chromatographic profile with the same range of low molecular weight (less than 17 kDa) in all analyzed samples by SEC; these results were also confirmed by MS showing an exact mass spectrum from 3 to 13 kDa. The fact that the peptide profiles were conserved during a six-month period at refrigeration conditions (2 to 8°C) maintaining the quality and stability of the immunomodulator supports the notion that it might be an alternative in the treatment of chronic hypersensibility disorders.
32197293 IL-35 and RANKL Synergistically Induce Osteoclastogenesis in RAW264 Mouse Monocytic Cells. 2020 Mar 18 Interleukin (IL)-35 is an immunosuppressive cytokine mainly produced by regulatory T cells. IL-35 mediates immunological functions by suppressing the inflammatory immune response. However, the role of IL-35 in bone-destructive diseases remains unclear, especially in terms of osteoclastogenesis. Therefore, the current study investigated the synergistic effect of IL-35 on osteoclastogenesis that is involved the pathogeneses of periodontitis and rheumatoid arthritis. Osteoclastic differentiation and osteoclastogenesis of RAW264 (RAW) cells induced by receptor activator of nuclear factor (NF)-κB ligand (RANKL) and IL-35 were evaluated by tartrate-resistant acid phosphate staining, hydroxyapatite resorption assays, and quantitative polymerase chain reaction. The effect of IL-35 on RANKL-stimulated signaling pathways was assessed by Western blot analysis. Costimulation of RAW cells by RANKL and IL-35 induced osteoclastogenesis significantly compared with stimulation by RANKL alone. Phosphorylations of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase tended to be increased by RANKL and IL-35 compared with RANKL or IL-35 alone. Additionally, the osteoclastogenesis induced by RANKL and IL-35 was suppressed by inhibition of ERK. In this study, IL-35 and RANKL induced osteoclastogenesis synergistically. Previous reports have shown that IL-35 suppresses the differentiation of osteoclasts. Therefore, IL-35 might play dual roles of destruction and protection in osteoclastogenesis.
31985640 The Risk of Complications after Carpal Tunnel Release in Patients Taking Acetylsalicylic A 2020 Feb BACKGROUND: Carpal tunnel release is one of the most common procedures in hand surgery. There is only scarce evidence regarding whether platelet inhibitors increase the risk of developing postoperative hemorrhage in carpal tunnel release. METHODS: This is a multicenter, propensity score-matched study including 635 carpal tunnel releases in 497 patients. Multivariate regression models were adjusted with the propensity score, which was developed to mitigate differences in patients with and without platelet inhibition with acetylsalicylic acid. Propensity score matching provides results close to the statistical quality of randomized controlled trials. The primary study endpoint was postoperative bleeding complication, defined as acute bleeding leading to reoperation or hematoma leading to physician visit. Patient satisfaction, functional outcome measured with the Boston Carpal Tunnel Questionnaire, and onset of surgical-site infection were also analyzed. RESULTS: Bleeding complications were observed in 56 procedures (8.8 percent). After propensity score matching, there was no significant difference between the patients with and without acetylsalicylic acid treatment (p = 0.997). History of thyroid disease (p = 0.035) and of rheumatoid arthritis (p = 0.026) were independent risk factors, whereas higher body mass index might have a beneficial effect (p = 0.006). Patients with postoperative bleeding had significantly impaired functional outcome as measured with the Boston Carpal Tunnel Questionnaire (p = 0.026). Median satisfaction in the investigated study population was 10 of 10 points and did not differ significantly between the antiplatelet and the non-antiplatelet cohorts (p = 0.072) CONCLUSION:: Carpal tunnel release under platelet inhibition with acetylsalicylic acid is safe and can be performed without interruption of such medication. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
31089006 Effectiveness and safety analysis of rituximab in 146 Indian pemphigus patients: A retrosp 2020 Jan BACKGROUND: Rituximab is being increasingly used for the treatment of pemphigus. Data derived from single-center studies following a uniform treatment protocol are limited. Effect of demography and disease type on treatment response is poorly characterized. OBJECTIVE: Our aim was to assess the effectiveness of biosimilar rituximab in pemphigus patients who had received rituximab as per rheumatoid arthritis protocol (2 doses, 1g each, infused 14 days apart). METHODS: It was a retrospective review of 146 eligible patients to assess the proportion of patients achieving complete remission off treatment, time to achieve complete remission off treatment, proportion of patients who relapsed after achieving complete remission off treatment, time taken to relapse, duration and total cumulative dose of corticosteroids administered after rituximab. Additionally, we tried to find whether a correlation existed between age, gender, total duration of illness before rituximab and pemphigus disease type with the above-mentioned outcome measures. RESULTS: Of 146 patients, 107 (73.3%) attained complete remission off treatment. Mean interval between first dose rituximab administration and complete remission off treatment was 6.6 ± 3.4months. Complete remission off treatment was sustained for a mean duration of 9.1 ± 8.5 months before relapse. Over a mean follow-up duration of 24.9 ± 17.1 months (median 23, maximum 68 months), 75 of 107 patients (76.5%) who had achieved complete remission after first cycle of rituximab relapsed. A mean total cumulative dose of 3496 ± 2496 mg prednisolone was prescribed over a mean duration of 7.2 ± 4.7 months after first cycle of rituximab. Time taken to achieve remission was significantly longer in pemphigus foliaceus and these patients required significantly higher cumulative dose of prednisolone over a longer duration after rituximab. No deaths and long-term complications were recorded. LIMITATIONS: Only clinical parameters were assessed. Immunological parameters including B-cell counts and enzyme-linked immunosorbent assay for anti-desmoglein antibody titers were not carried out. CONCLUSION: This study reinforces the beneficial role of rituximab in pemphigus. Pemphigus foliaceus patients required a higher total cumulative dose of prednisolone over a longer time to achieve remission and the remission lasted longer than that in pemphigus vulgaris.
34012869 Ayurvedic Balarista ameliorate anti-arthritic activity in adjuvant induced arthritic rats 2021 May BACKGROUND AND AIM: Balarista is a fermented ayurvedic liquid preparation recommended as a good therapy for the treatment of rheumatoid arthritis. In the present investigation, the anti-arthritic activity of in-house Balarista formulation and marketed M1, M2, M3 and M4 Balarista formulations at the dose of 2.31 ml/kg were studied on Complete Freund's adjuvant-induced arthritic rat model. EXPERIMENTAL PROCEDURE: Measurement of paw diameter, arthritic index, arthritic score, and body weight were made to assess the anti-arthritic activity. Alterations in hematological and biochemical parameters were carried out to ascertain the disease progression. The inflammatory mediators (TNF-α, IL-1β, and IL-6) were measured by the ELISA method. The oxidative stress parameters were evaluated in tissues of joint, liver, spleen and kidney. The histological and radiological changes in the ankle joint of rats were also studied. RESULTS AND CONCLUSION: Administration of in-house and marketed formulations exhibited significant anti-arthritic activity by reducing all the arthritic parameters. The anomalous alterations in hematological and biochemical parameters were remarkably restored. The expression level of serum pro-inflammatory cytokines was significantly suppressed in treated animals. The oxidative stress, indicated by an increase in lipid peroxidation, decreased in antioxidant enzyme i.e. superoxide dismutase and catalase along with non-enzymatic reduced glutathione in tissues, were strongly counteracted by the formulation. Abnormal changes in arthritic ankle joints shown by X-ray and histological examination were significantly protected by the formulation. The present study suggests that the administration of in-house and marketed Balarista formulations have produced a significant anti-arthritic effect by inhibiting free radicals and inflammatory cytokines.
33128728 Massive Demodicosis of the Eyes in a Patient with Sjögren Syndrome: A Case Report. 2021 Jun PURPOSE: Demodex mites infestation, typically asymptomatic, is a problem for patients with weakened immune systems because it often takes the form of symptomatic, massive infection. The Demodex mites play an important role in the occurrence of a range of eye surface diseases such as Demodex blepharitis, Meibomian gland dysfunctions, conjunctivitis and corneal changes. The ocular infection is closely related to the systemic invasion. Our goal was to minimize infestation and alleviate the symptoms of massive demodicosis so as to prevent further damage to the cornea. METHODS: Our research note involves a 61-year old woman diagnosed with secondary Sjögren syndrome due to rheumatoid arthritis. On the background of the autoimmune disease, corneal perforation of the left eye occurred that was cured by surgery. Then during the follow-up visit the patient was found (microscopically) massively infected with Demodex mites and the developed symptoms were particularly severe. RESULTS: Adequate dry eye syndrome and massive demodicosis therapy significantly reduced the number of Demodex mites and improved the patient's condition. CONCLUSION: We would like to draw the attention of the physicians of different specialties that special care should be taken with respect to the therapy of dry eye syndrome and ocular demodicosis in patients with immunological disorders to achieve therapeutic success and avoid particularly dangerous consequences of these diseases.
33091639 Musculoskeletal morbidity following spinal cord injury: A longitudinal cohort study of pri 2021 Jan BACKGROUND: People living with spinal cord injuries (SCIs) experience motor, sensory and autonomic impairments that cause musculoskeletal disorders following the injury and that progress throughout lifetime. The range and severity of issues are largely dependent on level and completeness of the injury and preserved function. OBJECTIVE: High risk of developing musculoskeletal morbidities among individuals after sustaining a traumatic SCI is well known in the clinical setting, however, there is a severe lack of evidence in literature. The objective of this study was to compare the incidence of and adjusted hazards for musculoskeletal morbidities among adults with and without SCIs. METHODS: Privately-insured beneficiaries were included if they had an ICD-9-CM diagnostic code for SCI (n = 9081). Adults without SCI were also included (n = 1,474,232). Incidence estimates of common musculoskeletal morbidities (e.g., osteoporosis, sarcopenia, osteoarthritis, fractures, etc.) were compared at 5-years of enrollment. Survival models were used to quantify unadjusted and adjusted hazard ratios for incident musculoskeletal morbidities. RESULTS: Adults living with traumatic SCIs had a higher incidence of any musculoskeletal morbidities (82.4% vs. 47.5%) as compared to adults without SCI, and differences were to a clinically meaningful extent. Survival models demonstrated that adults with SCI had a greater fully-adjusted hazard for any musculoskeletal morbidity (Hazard Ratio [HR]: 2.41; 95%CI: 2.30, 2.52), and all musculoskeletal disorders, and ranged from HR: 1.26 (1.14, 1.39) for rheumatoid arthritis to HR: 7.02 (6.58, 7.49) for pathologic fracture. CONCLUSIONS: Adults with SCIs have a significantly higher incidence of and risk for common musculoskeletal morbidities, as compared to adults without SCIs. Efforts are needed to facilitate the development of improved clinical screening algorithms and early interventions to reduce risk of musculoskeletal disease onset/progression in this higher risk population.
33052444 Menorrhagia due to uterine amyloidosis in familial Mediterranean fever: case-based review. 2021 Jan Amyloidosis is described by the deposition of misfolded proteins in the tissues. Amyloidoses are classified into two as systemic and localized. Out of the systemic forms, AL (light chain) amyloidosis is the most prevalent type; however, amyloid A (AA) amyloidosis is more frequently encountered in the rheumatology practice. AA amyloidosis stands out as a major complication of familial Mediterranean fever (FMF). Splenic and renal involvement is more likely in FMF-associated systemic amyloidosis. The involvement of thyroid and adrenal glands has also been described, although infrequently. Amyloidoses have a heterogeneous plethora of clinical manifestations, with certain phenotypes associated with specific amyloid forms. Gynecological amyloidosis is a rare condition. Uterine involvement may occur in a localized fashion or may also arise as a part of systemic involvement, albeit at a lesser ratio. Several cases of uterine AL amyloidosis have been documented so far as an organ involvement in systemic AL amyloidosis. On the other hand, uterine amyloidosis associated with AA amyloidosis has been described merely in one case with rheumatoid arthritis (RA). Here, we presented a 40-year-old female patient with FMF known for 38 years who underwent splenectomy and hysterectomy due to massive splenomegaly, deep anemia, and persistent menometrorrhagia. Histological examinations of materials revealed uterine and splenic AA amyloidosis. This case report is first-of-its-kind to describe FMF-associated uterine AA amyloidosis and also provides a discussion of possible mechanisms of amyloidosis-induced uterine bleeding.
32973504 The C-C Chemokine Receptor Type 4 Is an Immunomodulatory Target of Hydroxychloroquine. 2020 The emergence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) in China, reported to the World Health Organization on December 31, 2019, has led to a large global pandemic and is a major public health issue. As a result, there are more than 200 clinical trials of COVID-19 treatments or vaccines that are either ongoing or recruiting patients. One potential therapy that has garnered international attention is hydroxychloroquine; a potent immunomodulatory agent FDA-approved for the treatment of numerous inflammatory and autoimmune conditions, including malaria, lupus, and rheumatoid arthritis. Hydroxychloroquine has demonstrated promise in vitro and is currently under investigation in clinical trials for the treatment of COVID-19. Despite an abundance of empirical data, the mechanism(s) involved in the immunomodulatory activity of hydroxychloroquine have not been characterized. Using the unbiased chemical similarity ensemble approach (SEA), we identified C-C chemokine receptor type 4 (CCR4) as an immunomodulatory target of hydroxychloroquine. The crystal structure of CCR4 was selected for molecular docking studies using the SwissDock modeling software. In silico, hydroxychloroquine interacts with Thr-189 within the CCR4 active site, presumably blocking endogenous ligand binding. However, the CCR4 antagonists compound 18a and K777 outperformed hydroxychloroquine in silico, demonstrating energetically favorable binding characteristics. Hydroxychloroquine may subject COVID-19 patients to QT-prolongation, increasing the risk of sudden cardiac death. The FDA-approved CCR4 antagonist mogalizumab is not known to increase the risk of QT prolongation and may serve as a viable alternative to hydroxychloroquine. Results from this report introduce additional FDA-approved drugs that warrant investigation for therapeutic use in the treatment of COVID-19.
32948119 In silico drug discovery of IKK-β inhibitors from 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphe 2022 Feb The Inhibitor of IKK-β (nuclear factor kappa B kinase subunit beta), a specific modulator of NF-κB (nuclear factor-κB), is considered a valid target to discover new active compounds for various cancers and rheumatoid arthritis treatment. In this study a series of thirty 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl) pyridine derivatives was involved for a quantitative structure activity relationship model (QSAR) elaboration which allows the prediction of the pIC50 values of new designed compounds. The model can be used to predict the activity of new compounds within its applicability domain. Then a molecular docking study was carried out to identify the interactions between the compounds and the amino acids of the active site. After that, golden triangle, Veber's rule, and Lipinski's rule properties were calculated to identify the drug-likeness properties of the investigated compounds. Finally, in-silico-toxicity studies were performed to predict the toxicity of the new designed compounds. The analysis of the results of QSAR model and molecular docking succeeded to screen 21 interesting compounds with better inhibitory concentration having a good affinity to IKK-β. All compounds were within the range set by Veber's rule and Lipinski's rule. the analysis of golden triangle showed that the thirty 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl) pyridine derivatives would not have clearance and cell membrane permeability problems except comp6 comp12,comp20, comp21, and comp26.As for the new designed compounds, their properties may have these problems, except two compounds which are: A8m, A8p. The A1m, A1p, A3p and A11m compounds were predicted to be nontoxic. These findings indicate that the novel potent candidate drugs have promising potential to IKK-β enzyme inhibition and should motivate future experimental investigations.Communicated by Ramaswamy H. Sarma.
32788061 Persistent Wound Drainage among Total Joint Arthroplasty Patients Receiving Aspirin vs Cou 2020 Dec BACKGROUND: Persistent wound drainage (PWD) is one of the major risk factors for periprosthetic joint infections (PJI), arguably the most dreaded complications after a total hip and knee arthroplasty (THA and TKA). The aim of this study is to identify the rates of PWD among THA and TKA patients who received aspirin (ASA) or Coumadin for postoperative venous thromboembolism (VTE) prophylaxis. METHODS: Retrospective review of 5516 primary THA and TKA was performed. Patients with PWD were identified. Chi-square test was used to compare the incidences of PWD, 30-day VTE, and PJI at 6 months between the ASA and Coumadin groups. Multivariate regression model was used to identify independent risk factors for PWD using Charlson and Elixhauser comorbidity indexes. RESULTS: The prevalence of PWD was 6.4% (353/5516). Patients receiving ASA had lower incidence of PWD (3.2% vs 8.5%, P < .0001) while having comparable rates of 30-day VTE (1.3% vs 1.4%, P = .722) and PJI at 6 months (1.8% vs 1.4%, P = .233) compared to those receiving Coumadin. Risk factors for PWD were diabetes (odds ratio [OR], 19.3; 95% confidence interval [CI], 11.8-23.2), rheumatoid arthritis (OR, 15.3; 95% CI, 10.8-17.2), morbid obesity (OR, 13.2; 95% CI, 9.7-17.5), chronic alcohol use (OR, 3.5; 95% CI, 1.8-5.5), hypothyroidism (OR, 1.9; 95% CI, 1.1-3.2), and Coumadin (OR, 1.7; 95% CI, 1.2-2.2). CONCLUSION: Use of ASA is associated with significantly lower rates of PWD after THA and TKA when compared to Coumadin while being equally efficacious at preventing VTE. Coumadin was found to be an independent risk factor for PWD.
32632500 iTRAQ-based quantitative proteomic analysis of peripheral blood serum in piglets infected 2020 Jul 6 Porcine pleuropneumonia caused by Actinobacillus pleuropneumoniae (APP) is a swine respiratory disease with an important impact around the world either as a single infection or part of the porcine respiratory disease complex. The data of interaction between hosts and pathogens has becoming more crucial for exploration of the mechanism. However, up to now, comparatively little information is available on the systemic and dynamic changes that occur in pig serum in response to APP infection. This study used iTRAQ to identify differentially expressed proteins (DEPs) in pig serum in response to APP infection. Compared with the APP un-infected group (S0),there were 137 up-regulated and 68 down-regulated proteins at 24 h (S24), and 81 up-regulated and 107 down-regulated proteins at 120 h (S120). At 24 h, the immune response was not significantly enriched, but cell adhesion, cytosol, Golgi apparatus, GTP and ATP binding and regulation of cell cycle were extremely active, implying host preparation of immune response starting. Subsequently, innate immune response, negative regulation of apoptotic process, immunological synapse, adaptive immune response, the regulation of inflammatory response, positive regulation of T cell proliferation were more enhanced at 120 h then that of 24 h, representing innate immunity transferring to the adaptive, while endocytosis, cell adhesion and platelet aggregation showed obvious decline. The pathways of T cell receptor signaling pathway, cytokine-cytokine receptor interaction, complement and coagulation cascades, leukocyte transendothelial migration were active remarkably during all infection period, and more pathways could connect to form innate immune defense networks. Surprisingly, the pathways like amoebiasis, rheumatoid arthritis and malaria had been found up-regulated. As a conclusion, APP could delay host inflammatory response to the infection at early stage, and induced innate immunity to convert from adhesion, interaction into complement activation, proteasome digestion, bacterial invasion at later stage. This would increase our understanding of the porcine distinct response to APP infection.