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Alopecia areata (AA) is a T‐cell‐mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy—a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA‐affected scalp tissues and IFNγ and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFNγ and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFNγ and poly(I:C)‐induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN‐induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1‐mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is an autoimmune inflammatory disease characterized by non‐scarring hair loss due to an immune response that targets hair follicles. The current treatment approach for AA involves the use of immunosuppressants and immunomodulators to reduce cytokine levels around affected hair follicles. Sodium‐glucose cotransporter 2 (SGLT2) inhibitors have emerged as potential anti‐inflammatory agents with diverse beneficial effects in various medical conditions. This study investigates the role of beta‐hydroxybutyrate (BHB), a ketone body produced during SGLT2 inhibition, in the pathogenesis of AA. Serum BHB levels were found to be significantly elevated in patients with AA compared with healthy controls, with higher levels correlating with severity of hair loss. BHB treatment increased inflammatory cytokine production in outer root sheath (ORS) cells, mimicking the inflammatory conditions seen in AA. The results suggest that elevated BHB levels may exacerbate the inflammatory immune response in AA patients and may be associated with chronic hair loss and resistance to treatment. Serum BHB levels may serve as a potential marker of poor prognosis in patients with severe AA. Further research is needed to elucidate the precise role of BHB in the pathogenesis of AA and its implications for disease management. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients. Methods: We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome‐wide single‐nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well‐validated non‐HLA SNPs and HLA haplotypes of SLE‐risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration. Results: Childhood‐onset SLE (<16 years) conferred the highest genetic risk compared with adult‐onset (16–50 years) or late‐onset (>50 years) SLE (P = 6.8 × 10−6). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β = 0.143, P = 1.8 × 10−6). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio [HR] 1.74, P = 2.2 × 10−8) and anti–Sm antibody production (HR 1.85, P = 2.8 × 10−5). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10−5) and class V (HR 2.79, P = 1.0 × 10−3), but especially lupus nephritis class V in anti–Sm‐positive SLE (area under the curve 0.68, P = 1.8 × 10−4). Conclusion: Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti–Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients. [ABSTRACT FROM AUTHOR]

Keywords: acne; IGF-1; lipogenesis; sebocytes; YAP EN acne IGF-1 lipogenesis sebocytes YAP 996 998 3 07/14/23 20230701 NES 230701 Acne is a chronic inflammatory disorder of the pilosebaceous unit. From these results, we determined that IGF-1 increased YAP activity in sebocytes and YAP inhibition attenuated IGF-1-induced lipid production by preventing IGFR-mTOR signalling pathway. To investigate the mechanism of YAP inhibition on IGF-1-induced lipogenesis, we evaluated the protein expression of important transcription factors related to lipid production. [Extracted from the article]

Background: Dermal fibroblasts play a pivotal role in hair follicle regeneration during wound repair. Recently, dermal fibroblast‐conditioned medium (DFCM), which contains multi‐peptide factors (MPFs), has been used to promote wound repair. Aim: This study aimed to investigate the stimulatory effects of MPF‐containing DFCM on hair growth. Methods: MPF‐containing DFCM was prepared using human neonatal dermal fibroblasts. Outer root sheath (ORS) and dermal papilla (DP) cells were cultured in MPF‐containing DFCM. We examined the expression and secretion of growth factors and cytokines using quantitative polymerase chain reaction and a growth factor array. In addition, the effect of MPFs on β‐catenin activity was determined using the TOPflash assay. All experiments were repeated at least three times with separate batches of cells. Results: MPF‐containing DFCM increased keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) mRNA expression in ORS cells and KGF and VEGF mRNA expression in DP cells. When ORS cells were treated with MPF‐containing DFCM, the secretion of several growth factors, including EGF, VEGF, insulin‐like growth factor‐binding protein (IGFBP)‐4, IGFBP‐6, and fibroblast growth factor‐7, was increased in the cell‐cultured medium compared with that in control. Additionally, MPF‐containing DFCM increased the transcriptional activation of β‐catenin in DP cells. Conclusions: These results suggest that MPF‐containing DFCM might stimulate hair growth by inducing growth factors in ORS and DP cells and regulating β‐catenin in DP cells. [ABSTRACT FROM AUTHOR]

Despite their potent antitumor activity, clinical application of immune checkpoint inhibitors has been significantly limited by their poor response rates (<30%) in cancer patients, primarily due to immunosuppressive tumor microenvironments. As a representative immune escape mechanism, cancer‐derived exosomes have recently been demonstrated to exhaust CD8+ cytotoxic T cells. Here, it is reported that sulfisoxazole, a sulfonamide antibacterial, significantly decreases the exosomal PD‐L1 level in blood when orally administered to the tumor‐bearing mice. Consequently, sulfisoxazole effectively reinvigorates exhausted T cells, thereby eliciting robust antitumor effects in combination with anti‐PD‐1 antibody. Overall, sulfisoxazole regulates immunosuppression through the inhibition of exosomal PD‐L1, implying its potential to improve the response rate of anti‐PD‐1 antibodies. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the causes and risk of death in a large cohort of Korean patients with rheumatoid arthritis (RA). Methods: Patients in the Hanyang BAE (Bae registry of Autoimmune diseases for Epidemiology) RA cohort who fulfilled the American College of Rheumatology criteria were analyzed. A total of 2355 patients were enrolled from October 2001 to December 2015. Mortality data were derived by linking with data from the Korean National Statistical Office. Standardized mortality ratio was estimated by dividing observed deaths by expected number of deaths in the general population. Results: Over the observation period, 225 deaths were reported. Total age‐ and sex‐adjusted standardized mortality ratio was 1.65 (95% confidence interval 1.44‐1.87). The most common cause of death was malignancy (40 cases; 17.8%), followed by respiratory disease (38 cases; 16.9%) and cardiovascular disease (32 cases; 14.2%). Mortality rate and causes of death differed according to year and age of RA onset. Compared with survivors, individuals who died were more likely to be male, smokers, diagnosed with RA at an older age, and to have long disease duration, higher erythrocyte sedimentation rate and C‐reactive protein, higher rheumatoid factor positivity rate, more severe radiographic damage, and more comorbidities. Conclusion: The mortality rate of patients with RA remains higher than that of the general population. Therefore, to improve the survival of patients with RA, attention should be paid to the management of comorbidities as well as to the RA itself. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate whether the augmentation of CaP into the femoral head around the lag screw results in superior clinical and radiological outcomes of treatment of unstable trochanteric fractures using an intramedullary (IM) implant. Fifty-six consecutive patients with unstable trochanteric fractures who had been surgically treated with IM devices between 2014 and 2016 were prospectively reviewed and randomly divided into two groups based on the use of CaP degradable cements: 28 patients were assigned to the CaP group, while the other 28 patients were assigned to the control group (no use of CaP). Clinical evaluations and radiological analyses were conducted during a minimum of 2-year follow-up. No significant differences in the mean visual analogue scale for the hip pain scores and modified Harris Hip Scores were found between the CaP group and the controls at postoperative 2 months and 2 years. However, earlier walker ambulation was possible in the CaP group (10 ± 9 days) compared to the control group (13 ± 12 days) (P = 0.02). In radiological analysis, the CaP group showed significantly lower difference between tip-apex distance measured immediately after surgery and that measured at one-year follow-up compared to the control group (P = 0.012). No screw cut-out occurred in the CaP group, while one patient in the control group was reoperated for screw cut-out. The CaP augmentation into the femoral head around lag screw can reduce lag screw penetration, prevent screw cut-out beyond the femoral head, and facilitate early ambulation in elderly patients with unstable trochanteric fractures. [ABSTRACT FROM AUTHOR]

A two-stage genomewide association (GWA) analysis was conducted to investigate the genetic factors influencing ultraviolet (UV)-induced skin pigmentation in Korean females after UV exposure. Previously, a GWA study evaluating ~500 000 single nucleotide polymorphisms (SNPs) in 99 Korean females identified eight SNPs that were highly associated with tanning ability. To confirm these associations, we genotyped the SNPs in an independent replication study (112 Korean females). We found that a novel SNP in the intron of the WW domain-containing oxidoreductase (WWOX) gene yielded significant replicated associations with skin tanning ability (P-value = 1.16 × 10-4). To understand the functional consequences of this locus located in the non-coding region, we investigated the role of WWOX in human melanocytes using a recombinant adenovirus expressing a microRNA specific for WWOX. Inhibition of WWOX expression significantly increased the expression and activity of tyrosinase in human melanocytes. Taken together, our results suggest that genetic variants in the intronic region of WWOX could be determinants in the UV-induced tanning ability of Korean females. WWOX represents a new candidate gene to evaluate the molecular basis of the UV-induced tanning ability in individuals. [ABSTRACT FROM AUTHOR]