Telomerase prevents accelerated senescence in glucose-6-phosphate dehydrogenase (G6PD)-deficient human fibroblasts

Fibroblasts derived from glucose-6-phosphate dehydrogenase (G6PD)-deficient patients display retarded growth and accelerated cellular senescence that is attributable to increased accumulation of oxidative DNA damage and increased sensitivity to oxidant-induced senescence, but not to accelerated telomere attrition. Here, we show that ectopic expression of hTERT stimulates telomerase activity and prevents accelerated senescence in G6PD-deficient cells. Stable clones derived from hTERT-expressing normal and G6PD-deficient fibroblasts have normal karyotypes, and display no sign of senescence beyond 145 and 105 passages, respectively. Activation of telomerase, however, does not prevent telomere attrition in earlier-passage cells, but does stabilize telomere lengths at later passages. In addition, we provide evidence that ectopic expression of hTERT attenuates the increased sensitivity of G6PD-deficient fibroblasts to oxidant-induced senescence. These results suggest that ectopic expression of hTERT, in addition to acting in telomere length maintenance by activating telomerase, also functions in regulating senescence induction

EBV-encoded small RNA1 and nonresolving inflammation in rheumatoid arthritis

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by perpetuated inflammation in multiple joints. To date, there is no cure for RA, and the causal factor for non-resolving inflammation in RA remains unclear. In this study, we initially observed expression of Epstein–Barr virus-encoded small RNA1 (EBER1) in the synovial tissue of all five patients who showed nonresolving RA inflammation. By contrast, EBER1 was detected in the synovial tissue of only one out of seven patients with advanced osteoarthritis (OA; p < 0.01, Fisher’s exact test). To confirm this finding, we conducted a second study on synovial tissue samples taken from 23 patients with nonresolving RA inflammation and 13 patients with OA. All synovial samples from patients with nonresolving inflammation of RA showed positive expression of EBER1 (23/23, 100%), whereas none of the synovial samples from patients with OA showed expression of EBER1 (0/13, 0%; p < 0.001, by Fisher’s exact test). In vitro, transfection of RA synovial fibroblasts with EBER1 induced the production of interleukin-6. Taken together, these data strongly suggest that nonresolving RA inflammation is strongly related to the presence of EBER1, which might be, at least partially, responsible for synovial fibroblast interleukin-6 production

Comparative efficacy of Chinese herbal medicines for dialysis patients with uremic pruritus: A systematic review and network meta-analysis

Introduction: Uremic pruritus is common in dialysis patients and reduces their quality of life. Chinese herbal medicine has been effective in patients with this condition.Methods: We conducted a random-effects network meta-analysis to compare the efficacies of different Chinese herbal medicine treatments for uremic pruritus. Outcome measures including the overall effective rates, visual analog scale scores, C-reactive protein levels, and adverse drug reactions were analyzed.Results: The network meta-analysis retrieved 25 randomized controlled trials. Compared with conventional treatments alone, combination treatments with Xiao-Yang-Ke-Li was the most effective intervention in decreasing visual analog scale scores (mean difference −2.98, 95% mean difference −5.05 to −0.91) and levels of C-reactive protein (mean difference −5.01, 95% mean difference −7.27 to −2.75). Conventional treatment combined with Si-Wu Tang was superior to other therapeutic combinations when overall effective rates were determined. The best visual analog scale scores and overall effective rates were achieved by adjunctive treatment with the Touxie-Jiedu-Zhiyang decoction followed by uremic clearance granules; these treatments were the most beneficial for uremic pruritis.Conclusion: Our network meta-analysis provided the relative efficacies of different adjunctive Chinese herbal formulas. Adjunctive treatment with the Touxie-Jiedu-Zhiyang decoction was the best treatment for improving overall effective rates and reducing visual analog scores of uremic pruritus in dialysis patients.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=357656; Identifier: CRD42022357656

The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an 18F-FDG PET/CT Study in the Tropics

<p>Abstract</p> <p>Background</p> <p>Brown adipose tissue (BAT) has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) in people living in the tropics, where the influence of outdoor temperature was low.</p> <p>Methods</p> <p>¹⁸F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA) of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and ¹⁸F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature.</p> <p>Results</p> <p>Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (<it>p </it>= 0.043) and a higher TMA (<it>p </it>= 0.028) than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (<it>p </it>= 0.016).</p> <p>Conclusions</p> <p>Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.</p

Applying a Comprehensive Action Determination Model to Examine the Recycling Behavior of Taipei City Residents

With the occurrence of rapid global economic growth concerns about waste and its related effects on the environment are on the rise. There has been an increasing focus towards sustainable development and waste recycling as part of environmental sustainability strategies, and the encouraging of recycling behavior has received considerable attention from various environmental stakeholders. While numerous studies have used grounded theories such as the theory of planned behaviors and the norm activation model to examine environmental behaviors, a lack of consideration of other important variables in these studies has been revealed. This study aimed to address this gap by adopting the comprehensive action determination model, which comprises a wider group of influencing variables related to norms, intentions, situations, and habits. This model was tested using structural equation modelling with a sample of 386 valid questionnaires collected from Taipei City residents in the domain of recycling behaviors. Results indicated that awareness had a positive influence on personal norms towards recycling behaviors; social norms had a positive influence on personal norms towards recycling behaviors; attitudes had a positive influence on recycling intentions; social norms had a positive influence on recycling intentions; personal norms had a positive influence on recycling intentions; perceived behavior control had a positive influence on recycling intentions; recycling intentions had a positive influence on recycling behavior; and recycling habits had a positive influence on recycling behavior. However, findings did not support the positive impact of perceived behavioral control on recycling behavior

Case Report: Ribociclib-induced phototoxicity presented as dyschromia with subsequent bullae formation

Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, is a novel targeted therapy for advanced-stage breast cancer. Although ribociclib-induced cutaneous side effects have been previously noted, they have not been well documented. Herein, we present a case of ribociclib-induced phototoxicity, which manifested as dyschromia over sun-exposed forearms and neck initially and as bullae formation subsequently. A 71-year-old woman with metastatic breast cancer developed dyschromia after daily treatment with ribociclib (600 mg) for 7 months. Skin biopsy of the pigmented lesion revealed interface dermatitis with melanin incontinence and dyskeratotic cells and ballooning keratinocytes with loss of melanocytes in the basal layer. Further, clefting at the basal layer of epidermis was noted in a more hyperpigmented field. Fontana–Masson staining revealed melanophages in the dermis. Human Melanoma Black-45 staining revealed decreased melanocyte numbers in the epidermis above the cleft. Immunohistochemical analyses revealed activated CD1a+ epidermal Langerhans cells and infiltrating CD4+ and CD8+ T cells in the epidermis and dermis, thereby indicating type IV hypersensitivity that was associated with damage to keratinocytes and melanocytes. To prevent progression of bullous dermatitis, we advised the patient to discontinue ribociclib and prescribed oral and topical prednisolone. Due to the risk of phototoxicity, we educated the patient on sun-protection strategies. The patient’s skin lesions subsided during the 2 months of treatment. Phototoxicity with dyschromia is a rare but significant ribociclib-induced cutaneous side effect. Early diagnosis, rapid ribociclib withdrawal, protection from sunlight, and prompt treatment are critical for preventing subsequent severe bullous dermatosis

Differential expression of GABAA receptor subunits δ and α6 mediates tonic inhibition in parvalbumin and somatostatin interneurons in the mouse hippocampus

Inhibitory γ-aminobutyric acid (GABA)-ergic interneurons mediate inhibition in neuronal circuitry and support normal brain function. Consequently, dysregulation of inhibition is implicated in various brain disorders. Parvalbumin (PV) and somatostatin (SST) interneurons, the two major types of GABAergic inhibitory interneurons in the hippocampus, exhibit distinct morpho-physiological properties and coordinate information processing and memory formation. However, the molecular mechanisms underlying the specialized properties of PV and SST interneurons remain unclear. This study aimed to compare the transcriptomic differences between these two classes of interneurons in the hippocampus using the ribosome tagging approach. The results revealed distinct expressions of genes such as voltage-gated ion channels and GABAA receptor subunits between PV and SST interneurons. Gabrd and Gabra6 were identified as contributors to the contrasting tonic GABAergic inhibition observed in PV and SST interneurons. Moreover, some of the differentially expressed genes were associated with schizophrenia and epilepsy. In conclusion, our results provide molecular insights into the distinct roles of PV and SST interneurons in health and disease

Activations of Both Extrinsic and Intrinsic Pathways in HCT 116 Human Colorectal Cancer Cells Contribute to Apoptosis through p53-Mediated ATM/Fas Signaling by Emilia sonchifolia Extract, a Folklore Medicinal Plant

Emilia sonchifolia (L.) DC (Compositae), an herbaceous plant found in Taiwan and India, is used as folk medicine. The clinical applications include inflammation, rheumatism, cough, cuts fever, dysentery, analgesic, and antibacteria. The activities of Emilia sonchifolia extract (ESE) on colorectal cancer cell death have not been fully investigated. The purpose of this study explored the induction of apoptosis and its molecular mechanisms in ESE-treated HCT 116 human colorectal cancer cells in vitro. The methanolic ESE was characterized, and γ-humulene was formed as the major constituent (63.86%). ESE induced cell growth inhibition in a concentration- and time-dependent response by MTT assay. Apoptotic cells (DNA fragmentation, an apoptotic catachrestic) were found after ESE treatment by TUNEL assay and DNA gel electrophoresis. Alternatively, ESE stimulated the activities of caspase-3, -8, and -9 and their specific caspase inhibitors protected against ESE-induced cytotoxicity. ESE promoted the mitochondria-dependent and death-receptor-associated protein levels. Also, ESE increased ROS production and upregulated the levels of ATM, p53, and Fas in HCT 116 cells. Strikingly, p53 siRNA reversed ESE-reduced viability involved in p53-mediated ATM/Fas signaling in HCT 116 cells. In summary, our result is the first report suggesting that ESE may be potentially efficacious in the treatment of colorectal cancer