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The study was designed to detect the expression and clinical significance of the HEATR3 gene in bladder cancer (BCa) and to preliminarily explore whether this gene can affect the occurrence and development of BCa through the AKT/ERK signaling pathway. The expression and prognostic value of HEATR3 were explored based on The Cancer Genome Atlas (TCGA) and Genotypic Tissue Expression (GTEx) databases. Microarray immunohistochemical analysis was performed in 30 BCa cases to investigate the level of HEATR3 protein and to explore the relationship between HEATR3 and the clinicopathological features of BCa. Western Blot and qRT-PCR were used to detect HEATR3 protein and mRNA in BCa cell lines (5637, TCCSUP, SW780) and fallopian tube epithelial cell (SV-HUC-1). CCK8 method was employed to study the proliferation of BCa cells after heat treatment. Transwell assay was conducted to analyze the effect of HEATR3 on cell migration and invasion. And cell cycle and apoptosis were detected by flow cytometry. Furthermore, Western Blot assay was used to probe the effects of down-regulation of HEATR3 expression on the expression and phosphorylation levels of AKT and ERK proteins in BCa cells. Bioinformatics analysis showed that HEATR3 was significantly up-regulated in BCa, and high HEATR3 expression was associated with poor prognosis of BCa patients. In vitro experiments demonstrated that HEATR3 expression was up-regulated in BCa tissues compared with that in adjacent tissues. HEATR3 protein was also up-regulated in malignant cell lines. HEATR3 knockdown in BCa cells could inhibit cell proliferation, invasion and migration, block cell cycle and promote cell apoptosis. At the same time, HEATR3 knockdowns reduced the expression levels of p-AKT and p-ERK proteins. HEATR3 knockdown inhibits the development of BCa cells through the AKT/ERK signaling pathway. and it may become one of the most promising molecular targets for BCa treatment. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) exhibits difference in immune polarization between Caucasians and Asian races due to which an evaluation of the efficacy and safety of Pimecrolimus (PIM) in Asian population is called for. The current study addresses the need via a sub-group analysis of the PETITE study (NCT00120523) to evaluate the safety and efficacy of PIM in Chinese infants. Patients with AD (≥3 months–<12 months of age) were randomized in a 1:1 ratio to either PIM 1% cream or topical corticosteroids (TCS). The primary endpoint was safety. The secondary endpoint was efficacy. 120 patients were randomized to either PIM 1% or TCS (n = 61 for PIM, n = 59 for TCS). The most often reported adverse events were reported by similar proportions of patients treated with PIM or TCS. There was a progressive increase in overall IGA treatment success in infants treated with PIM (82.9%, p <.05, 95% CI: 70.4, 95.3) after 26 weeks which was comparable to the TCS group (88.5%, p <.05, 95% CI: 79.8, 97.1). PIM showed an early and sustained efficacy in the Chinese sub-population with a substantial corticosteroid-sparing effect in patients with AD. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the frequency of very important pharmacogenomic (VIP) genes varies in different populations which leads to the diversities in drug efficacy, safety, and the risk associated with adverse drug reactions (ADRs). The purpose of this study was to identify the distribution differences of VIP variants between the Li population and the other 13 populations. Based on the Pharmacogenomics Knowledgebase database (PhamGKB), we successfully genotyped 52 VIP variants within 27 genes in 200 unrelated Li population. χ2 test was used to evaluate the significant differences of genotype and allele frequencies between the Li and the other 13 populations from 1000 Genomes Project. Our study showed that the genotype frequencies of single nucleotide polymorphisms (SNPs) on KCNH2, ACE, CYP4F2, and CYP2E1 were considerably different between Li and the other 13 populations, especially in rs1805123 (KCNH2), rs4291 (ACE), rs3093105 (CYP4F2), and rs6413432 (CYP2E1) loci. Meanwhile, we found several VIP variants that might alter the drug metabolism of cisplatin-cyclophosphamide (CYP2E1), vitamin E (CYP4F2), asthma amlodipine, chlorthalidone, and lisinopril (ACE) through PharmGKB. We also identified other variants which were associated with adverse effects in isoniazid and rifampicin (CYP2E1; hepatotoxicity). The four loci rs1805123 (KCNH2), rs4291 (ACE), rs3093105 (CYP4F2), and rs6413432 (CYP2E1) provided a reliable basis for the prediction of the efficacy of certain drugs. The study complemented the existed pharmacogenomics information, which could provide theoretical basis for predicting the efficacy of certain drugs in the Li population. [ABSTRACT FROM AUTHOR]

• Our study found several SNPs related to pharmacogenetics among Lahu population. • The rs20417, rs776746, rs2115819, and rs3093105 variants are different in the Lahu. • The genotype frequency of the SNPs are associated with metabolism of drugs. • It will help optimize drug dose and recommend appropriate drugs for Lahu patients. Pharmacogenomics has been widely used to study the very important pharmacogenetic (VIP) variants among populations, but information on pharmacogenomics in the Lahu population is limited. The purpose of this study was to determine the differences in the distribution of VIP variants between the Lahu and the other 26 populations. We genotyped 55 VIP variants of 27 genes in the Lahu population from the PharmGKB database. χ2 test was used to compare the genotype and allele frequencies between the Lahu and the other 26 populations from the 1000 Genomes Project. The genotype and allele frequencies of single nucleotide polymorphisms (SNPs) on rs20417 (PTGS2), rs776746 (CYP3A5), rs2115819 (ALOX5), and rs3093105 (CYP4F2) were considerably different in the Lahu population compared with those in the other 26 populations. Besides, based on the PharmGKB database, we identified several VIP variants that may alter the drug metabolism of aspirin (PTGS2), tacrolimus (CYP3A5), montelukast (ALOX5), and vitamin E (CYP4F2). The results show that there are significant differences in the genotype frequency distribution between the Lahu and the other 26 populations. Our study supplements the pharmacogenomics information of the Lahu population and provides a theoretical basis for individualized medicine in Lahu. [ABSTRACT FROM AUTHOR]

20 patients with systemic contact dermatitis due to nickel are described. Of these patients, 15 were female and 5 were male. Their mean age was 24·8 years (16–51 years). All had experienced contact dermatitis in the umbilical area due to continual contact with metal belt-buckles or buttons. Then, with long- or short-term aggravation of such periumbilical dermatitis, commonly in summer, lesions spread to other sites such as the side of the neck, the flexures of the extremities, etc. All patients showed a positive patch test to nickel sulphate (2·5% in petrolatum) and the dimethylglyoxime test demonstrated the presence of free nickel on metal buttons or belt-buckles. Punch biopsies performed in 7 patients showed subacute dermatitis. After avoidance of continual exposure to objects containing nickel and foods rich in nickel, as well as treatment with oral antihistamines and topical corticosteroids, all patients improved or cleared. It has been reported that nickel can cause systemic contact dermatitis by some internal systemic route, such as oral intake, transfusion, inhalation, implantation of metal medical devices, etc. In our patients, we found that continual local skin contact could also elicit systemic contact dermatitis. [ABSTRACT FROM AUTHOR]

A 33-year-old Chinese male with a 28-year history of atopic dermatitis (AD) presented to our clinic for persisted AD lesions with more frequent flares. Nevertheless, the overall treatment result of dupilumab was rather satisfied with significant improvements of patient's AD lesions (Figure 1P-T), pruritus and quality of life during 30-week follow-up (EASI = 1.7, NRS pruritus = 2/10, DLQI = 8). [Extracted from the article]

Background: Treatment of chronic prurigo (CPG) is challenging. As an antagonist of IL-4R, dupilumab has shown effectiveness in treating CPG in several clinical studies. Recently, the US Food and Drug Administration (FDA) approved dupilumab for the treatment of prurigo nodularis (PN). Objectives: The purpose of this study was to examine the efficacy of dupilumab in Chinese patients with CPG, and to analyze the difference in response between subtypes of CPG. Methods: This retrospective study included 18 patients with CPG who were treated with dupilumab for at least 16 weeks from March 2022 to October 2022. Disease severity and patient self-assessment questionnaires were assessed at baseline and each visit, including the peak Pruritus Visual Analogue Scale (PP-VAS), Prurigo Activity and Severity Score (PAS), Investigator Global Assessment (IGA), Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS) and Itchy-specific Quality of Life questionnaire (ItchyQoL). Results: After 2 weeks of dupilumab treatment, pruritus scores were significantly reduced as measured by PP-VAS scores. Prurigo Activity and Severity scores decreased significantly at Week 2, whereas IGA improved significantly at Week 8. The DLQI, HADS, and ItchyQoL scores at Week 16 also showed significant improvement from baseline. Patients in all subtypes showed improvement in pruritus and lesion severity. Conclusions: Dupilumab was effective in improving pruritus and lesions in patients with various subtypes of CPG. [ABSTRACT FROM AUTHOR]

Focal dermal hypoplasia (FDH) is an X-link dominant multisystemic disorder affecting both ectodermal and mesodermal tissues, which is usually characterized by patchy dermal hypoplasia, herniation of subcutaneous fat into the dermis, papillomas, dystrophic nails, and skeletal abnormalities.[1] I PORCN i was identified as the causative gene for FDH.[2] To date, 185 mutations in I PORCN i have been found in FDH patients, mostly within the I PORCN i gene coding sequence. Slightly fatty herniations on the left lumbar (Figure 1c), dystrophic nails (Figure 1d), and enamel hypoplasia of incisors were also observed but without abnormal growth or intelligence. [Extracted from the article]

The cGAS-STING signaling pathway senses the presence of cytosolic DNA, induces strong type I interferon responses, and enhances inflammatory cytokine production, placing it as an important axis in infection, autoimmunity, and tumor immunity. Recent studies have shown that the abnormalities and/or dysfunctions of cGAS-STING signaling are closely related to the pathogenesis of skin diseases and/or cancers. Additionally, a variety of new therapeutics targeting the cGAS-STING signaling are in development for the treatment of skin disorders. However, the precise molecular mechanisms of cGAS-STING-mediated cutaneous disorders have not been fully elucidated. In this review, we will summarize the regulatory roles and mechanisms of cGAS-STING signaling in skin disorders and recent progresses of cGAS-STING-related drugs as well as their potential clinical applications. [ABSTRACT FROM AUTHOR]

Acne is a chronic inflammatory skin disorder that profoundly impacts the quality of life of patients worldwide. While it is predominantly observed in adolescents, it can affect individuals across all age groups. Acne pathogenesis is believed to be a result of various endogenous and exogenous factors, but the precise mechanisms remain elusive. Recent studies suggest that dysbiosis of the skin microbiota significantly contributes to acne development. Specifically, Cutibacterium acnes, the dominant resident bacterial species implicated in acne, plays a critical role in disease progression. Various treatments, including topical benzoyl peroxide, systemic antibiotics, and photodynamic therapy, have demonstrated beneficial effects on the skin microbiota composition in acne patients. Of particular interest is the therapeutic potential of probiotics in acne, given its direct influence on the skin microbiota. This review summarizes the alterations in skin microbiota associated with acne, provides insight into its pathogenic role in acne, and emphasizes the potential of therapeutic interventions aimed at restoring microbial homeostasis for acne management. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis ( AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine ( TARC) is overproduced in AD patients, and its serum levels are significantly higher in individuals with AD than in those with other inflammatory skin diseases. Objectives The purpose of this study was to examine whether serum levels of TARC can assess the severity of AD and be used in the clinical evaluation of AD. Methods A total of 73 AD patients, 11 patients with generalized atopic eczema ( AE), and 30 healthy control subjects were enrolled. SCORAD ( SCORing of Atopic Dermatitis) indices were calculated according to skin symptom scores. The Th2 chemokines TARC kit was then used to obtain serum TARC values in each group. Finally, statistical analysis was used to identify any correlations between serum TARC level and SCORAD index in AD and AE patients. Results Mean serum TARC values were 159.95 in healthy controls, 146.46 in the mild AD group, 202.71 in the moderate AD group, 1216.61 in the severe AD group and 1554.50 in the severe AE group. The serum TARC level was significantly correlated with SCORAD score in AD patients ( P < 0.01). However, there was no significant correlation between SCORAD score and TARC in AE patients ( P = 0.610). Conclusions The serum TARC level can be used to assess the severity of AD and as a reference index for the fast clinical evaluation of AD. [ABSTRACT FROM AUTHOR]

This article reports on a case of allergic contact dermatitis caused by benzalkonium chloride (BAK) from a laundry disinfectant in a Chinese patient. The patient experienced diffuse skin erythema and severe pruritus, initially misdiagnosed as atopic dermatitis. The rash improved after discontinuing the disinfectant and tapering off medication. Patch testing confirmed the diagnosis of allergic contact dermatitis to BAK. This case highlights the importance of considering contact allergens in laundry care products, such as BAK, in cases of textile-related dermatitis. [Extracted from the article]

Recently, multiple clinical trials of novel drugs for chronic pruritus or prurigo are in progress and show good responses, such as nemolizumab, dupilumab, and serlopitant.3,4 Here, we report a case of refractory PN successfully treated with selective Janus Kinase (JAK) inhibitor baricitinib. It has been also confirmed that the disruption of neuronal JAK1 signaling reduces chronic itch, indicating the therapeutic effect of JAK inhibitor in PN patients.7 Successful therapeutic cases of prurigo with JAK inhibitor, such as baricitinib used in a case of prurigo-type AD, and tofacitinib used in chronic pruritus patients and recalcitrant PN, were reported previously.8-10 In summary, we report a case of MTX intolerant non-atopic PN patient who responded well to baricitinib, particularly in the rapid relief of pruritus. Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by severe itching and nodular lesions with uncertain etiology and pathogenesis.1 Previous studies show that PN is related to vicious cycles of chronic pruritus and repeated scratching, so rapid itch control is the core element of PN treatment.2 However, there are currently no medications approved for PN, which leads to highly variable practices in the prescription of off-label medications, including topical therapy, phototherapy, and systemic therapy (immunosuppressants, gabapentioids, thalidomide, antidepressants, etc.). [Extracted from the article]

The expression of IL-2RA and IL-2RB was correlated with breast cancer (BC) progression. However, there is no literature investigating the association of IL-2RA and IL-2RB polymorphisms with BC predisposition among Chinese Han Women. Seven SNPs in IL-2RA and IL-2RB were genotyped by Agena MassARRAY platform among 553 BC patients and 550 healthy controls. Odds ratios (OR) and 95% confidence interval (CI) adjusted for age were calculated for the effect of IL-2RA and IL-2RB variants on BC susceptibility. IL-2RA rs12722498 was a protective factor for BC occurrence (OR = 0.70, p = 0.019), especially in subjects with age ≤ 52 years (OR = 0.55, p = 0.004). IL-2RA rs12569923 (OR = 9.07, p = 0.033), IL-2RB rs2281089 (OR = 0.67, p = 0.043) and rs9607418 (OR = 0.59, p = 0.012) were related to the incidence of estrogen receptor positive (ER +) BC. IL-2RB rs3218264 (OR = 1.38, p = 0.010) and rs9607418 (OR = 0.56, p = 0.009) were associated with the risk of developing progesterone receptor positive (PR +) BC. Rs2281089 (OR = 1.54, p = 0.012) and rs1573673 (OR = 0.72, p = 0.035) were correlated to Ki-67 level. Moreover, IL-2RB rs2281089 (OR = 0.72, p = 0.022) showed a reduced risk of BC metastasis, and IL-2RA rs12722498 (OR = 0.54, p = 0.030) had a lower frequency in BC patients with tumor size > 2 cm. Our study identified the potential effect of genetic variations in IL-2RA and IL-2RB on BC susceptibility and/or BC clinicopathologic indicators among Chinese Han Women. [ABSTRACT FROM AUTHOR]

Lichen planopilaris (LPP), an uncommon inflammatory scalp disorder resulting in scarring of alopecia on the scalp, was challenging in treatment due to poor responses to available therapies.1 In this letter, we reported a case of LPP improved with oral baricitinib. The histopathology of an alopecia patch at low magnification, Hematoxylin-Eosin stain 10× (B), and at high magnification, Hematoxylin-Eosin stain 40× (C). gl GLO:ETZ/01nov22:dth15882-fig-0002.jpg PHOTO (COLOR): 2 The changes in dermoscopy examination during the treatment of baricitinib: before treatment (A), after treatment with a dosage of 4 mg daily for 3 months (B), and continuous treatment with a dosage of 2 mg daily for 6 months (C). Physical examination showed erythematous alopecia patches on the scalp's parietal areas, with perifollicular erythema and follicular hyperkeratosis at the margins of expanding alopecic patches (Figure 1A). [Extracted from the article]

Summary: Hyaluronic acid (HA) is now extensively employed for esthetic concerns. In the majority of cases, HA is considered to be safe, but mild‐to‐severe complications can occur in a few cases. Hyaluronidase is enzymes that degrade HA, also being suggested for the treatment of HA filler‐induced complications. However, hyaluronidase has been reported to be a potential cause of allergic responses in some anesthetic and ophthalmic literature. However, there are few reports of allergic reactions to hyaluronidase in cosmetic medicine. We herein report on a 39‐year‐old Asian woman who developed a delayed allergic hypersensitivity to hyaluronidase in the treatment process of HA‐related granulomatous reaction. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNAs) have been reported to circulate in the blood in a highly stable and cell‐free form. Dysregulated expression of miRNAs has been detected in various pathological conditions including atopic dermatitis. In our study, human blood plasma miRNAs were identified by high‐throughput sequencing and compared among patients of atopic dermatitis and healthy controls. We found that miR‐151a was differentially expressed in the plasma of atopic dermatitis patients. MiR‐151a regulates the expression of IL12RB2 by targeting two loci in the 3′ untranslated region of the Il12rb2 gene. Moreover, IL12RB2 was remarkably downregulated in Jurkat cells overexpressing miR‐151a. Jurkat cells treated with phytohemagglutinin also showed reduced expression of IFN‐γ, interleukin‐2 (IL‐2) and IL‐12. Together, these results suggest that miR‐151a is involved in the pathogenesis of atopic dermatitis by regulating IL12RB2. [ABSTRACT FROM AUTHOR]

Summary: Background: Ultraviolet (UV) B irradiation is known to suppress contact hypersensitivity (CHS) responses in mouse models by suppressing immune responses. However, the cellular mechanisms responsible for UVB‐induced systemic suppression remain unclear. Regulatory B cells have been reported to play an inhibitory role during CHS. It is presently unknown whether regulatory B cells contribute to the effect of UVB phototherapy. Objective: To investigate the inductive effect of UVB on regulatory B cells and the underlying mechanisms by using a CHS mouse model. Methods: CHS was induced with oxazolone, and evaluated by histopathology, flow cytometry, and quantitative real‐time polymerase chain reaction. Result: We found that UVB irradiation induced regulatory B cell expansion and ameliorated CHS. UVB‐induced regulatory B cells contribute to systemic immunosuppression by inhibiting the proliferation of T cells. Moreover, we determined that toll‐like receptor (TLR) 4, the expression of which was upregulated in B cells after UVB exposure, played an essential role in the induction of regulatory B cells. Conclusion: Our data identified regulatory B cells as regulators of UVB‐induced immunosuppression in CHS, and suggest the importance of the UVB–TLR4 axis in the generation of regulatory B cells. [ABSTRACT FROM AUTHOR]

Der p 2, a major allergen derived from the house dust mite Dermatophagoides pteronyssinus , is one of the most clinically relevant allergens worldwide. Recombinant Der p 2 (rDer p 2) is useful in clinical diagnosis and disease-specific immunotherapy. However, previous studies showed that Der p 2 can only be expressed in Escherichia coli ( E. coli ) cells as inclusion bodies, thus protein refolding is required to obtain functional products. Here we report a new method to produce biologically active Der p 2 protein in E. coli . N-terminal hexahistidine- and trigger factor (TF)-tagged Der p 2 was expressed in soluble form in E. coli and purified using a combination of chromatography processes. This procedure produced milligram-level high purity Der p 2 per liter of bacterial culture. Moreover, far-UV region circular dichroism (CD) analysis and serum specific IgE reactivity test demonstrated that the secondary structure and IgE reactivity properties of rDer p 2 produced in our study were almost identical to those of natural Der p 2 (nDer p 2). In conclusion, the method developed in this work provides a useful tool for the production of immunologically active recombinant Der p 2 for clinical applications. [ABSTRACT FROM AUTHOR]

Background: Impaired Toll-like receptor 2 (TLR2) function has been associated with the pathogenesis of atopic dermatitis (AD). However, there are only few studies reporting on the TLR2-induced immunological responses of circulating leucocytes of AD patients. We thus investigated the expression and secretion of Th1, Th2 and Th17/22 cytokines triggered by TLR2 ligands in human peripheral blood mononuclear cells (PBMCs) from AD patients. Expression of TLR2, 1, 6 and high-affinity receptor for IgE (FcεRI) were further investigated to evaluate the outcome of immune response in AD.Methods: Expression of TLR2, 1, 6 and FcεRI in PBMCs from AD patients and healthy individuals were measured by qPCR. Subsequent to stimulation with TLR2 ligands PGN and Pam3CSK4, expression and secretion of Th1, Th2 and Th17/22 cytokines were investigated by qPCR and ELISA.Results: The levels of TLR2, 1, 6 mRNA were not altered in both groups of subjects while that of FcεRI was increased in AD patients. Subsequent to the activation by TLR2 ligands, PBMCs from AD patients significantly released less IFN-γ, IL-17F and IL-22 than those from healthy controls while no detectable level of release was observed with the other cytokines. In contrast, significantly higher levels of mRNA expression for TNF-α, IL5, IL-17A and IL-22 were observed in TLR2 activated PBMCs of AD patients than those of healthy control.Conclusions: PBMCs from AD patients are defective in the secretion of Th1 and Th17/22 cytokines in response to TLR2 ligands. The inconsistent increased expression of the mRNA for the corresponding Th1 cytokines and the Th2 cytokines IL-5 suggested that there may be alterations of downstream signaling events in the cytokine release mechanisms of PBMCs that are associated with the development of AD. [ABSTRACT FROM AUTHOR]