A case report of extra-articular manifestation of rheumatoid arthritis: Rheumatoid nodules in lungs.

Rheumatoid arthritis is a systemic inflammatory disorder primarily affecting joints but not limited to the joints alone. Extra-articular manifestations involve skin, ocular, gastrointestinal, pulmonary, cardiac, renal, neurological, and hematological systems. Among them, skin manifestations (20%) are most common, presenting as nodules on the extensor surfaces of the upper and lower extremities. In rare cases these nodules can also be detected within the heart and lungs. Interestingly, rheumatoid nodules are often seen in patients on leflunomide, methotrexate, or tumor necrosis factor-alpha antagonists. Nevertheless, definitive diagnosis requires a histopathological analysis. In this case report, we presented a 49-year-old male patient with a relatively short period of disease activity leading to rheumatoid nodules in the lungs. Considering the ongoing COVID-19 pandemic and that tuberculosis was still endemic in Kazakhstan, achieving the definite diagnosis was challenging. Initial imaging study revealed bilateral polysegmental pneumonia. The tests for COVID-19 and pulmonary tuberculosis were negative. A follow-up chest computed tomography scan had signs of disseminated lung lesions of unknown origin. Lung biopsy showed a morphological picture of productive granulomas characteristic for tuberculosis. However, at the second look, typical scarring granulomas typically seen in rheumatoid nodules were observed.

Epidemiology of tuberculosis in Kazakhstan: data from the Unified National Electronic Healthcare System 2014-2019.

OBJECTIVES: This study aims to estimate tuberculosis (TB) incidence, mortality rates and survival HRs in Kazakhstan, using large-scale administrative health data records during 2014-2019. DESIGN: A retrospective cohort study. SETTINGS: Data for patients with TB in Kazakhstan during 2014-2019, reported in the Unified National Electronic Healthcare System. PARTICIPANTS: Patients with TB in Kazakhstan (ICD-10 (The International Classification of Diseases, 10th revision) codes: A15-A19). OUTCOME MEASURES: Demographic factors, diagnoses and comorbidities were analysed using descriptive, bivariate and multivariable statistical analyses. TB incidence and mortality rates were calculated, and Cox regression and Kaplan-Meier survival analysis were performed to assess risk factors for survival rates. RESULTS: Of the 149 122 patients with TB, 91 437 (61%) were males, and 139 931 (94%) had respiratory TB. From 2014 to 2019, TB incidence declined from 227 to 15.2 per 100 000 individuals, while all-cause mortality increased from 8.4 to 15.2 per 100 000. Age-specific TB incidence was lowest for 0-10 years of age and highest for 20 years of age. Being older, man, urban residence versus rural, retired versus employed, having HIV and having diabetes versus no comorbidities were associated with lower survival rates. CONCLUSION: To date, this is the largest TB published study for Kazakhstan, characterising TB incidence and mortality trends by demographic factors, and risk factors for survival rates. The findings highlight the need for targeted interventions to address the growing burden of TB, particularly among older adults, men, urban residents and those with HIV and diabetes. The study underscores the importance of using administrative health data to inform policy and health system responses to TB in Kazakhstan.

Role of periostin in inflammatory bowel disease development and synergistic effects mediated by the CCL5-CCR5 axis.

Inflammatory bowel disease (IBD), comprising mainly Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract. In recent years, a wealth of data has been accumulated demonstrating the complex interplay of many different factors in the pathogenesis of IBD. Among these are factors impacting the epithelial barrier function, including vessel and extracellular matrix (ECM) formation, the gut microbiome (e.g., bacterial antigens), and, most importantly, the production of cytokines (pro- and anti-inflammatory) directly shaping the immune response. Patients failing to resolve the acute intestinal inflammation develop chronic inflammation. It has been shown that the expression of the matricellular protein periostin is enhanced during IBD and is one of the drivers of this disease. The C-C chemokine receptor 5 (CCR5) is engaged by the chemotactic mediators CCL3/MIP-1α, CCL4/MIP-1ß, and CCL5/RANTES. CCR5 blockade has been reported to ameliorate inflammation in a murine IBD model. Thus, both periostin and CCR5 are involved in the development of IBD. In this study, we investigated the potential crosstalk between the two signaling systems and tested a highly potent CCL5 derivative acting as a CCR5 antagonist in a murine model of IBD. We observed that the absence of periostin influences the CCR5-expressing cell population of the gut. Our data further support the notion that targeted modulation of the periostin and CCR5 signaling systems bears therapeutic potential for IBD.

Analysis of origin and protein-protein interaction maps suggests distinct oncogenic role of nuclear EGFR during cancer evolution.

Receptor tyrosine kinase EGFR usually is localized on plasma membrane to induce progression of many cancers including cancers in children (Bodey et al. In Vivo. 2005, 19:931-41), but it contains a nuclear localization signal (NLS) that mediates EGFR nuclear translocation (Lin et al. Nat Cell Biol. 2001, 3:802-8). Here we report that NLS of EGFR has its old evolutionary origin. Protein-protein interaction maps suggests that nEGFR pathways are different from membrane EGFR and EGF is not found in nEGFR network while androgen receptor (AR) is found, which suggests the evolution of prostate cancer, a well-known AR driven cancer, through changes in androgen- or EGF-dependence. Database analysis suggests that nEGFR correlates with the tumor grades especially in prostate cancer patients. Structural predication analysis suggests that NLS can compromise the differential protein binding to EGFR through stretch linkers with evolutionary mutation from N to V. In experiment, elevation of nEGFR but not membrane EGFR was found in castration resistant prostate cancer cells. Finally, systems analysis of NLS and transmembrane domain (TM) suggests that NLS has old origin while NLS neighboring domain of TM has been undergone accelerated evolution. Thus nEGFR has an old origin resembling the cancer evolution but TM may interfere with NLS driven signaling for natural selection of survival to evade NLS induced aggressive cancers. Our data suggest NLS is a dynamic inducer of EGFR oncogenesis during evolution for advanced cancers. Our model provides novel insights into the evolutionary role of NLS of oncogenic kinases in cancers.