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Macrophages serve as a pivotal nexus in the pathogenesis of acne vulgaris, orchestrating both the elimination of Cutibacterium acnes (C. acnes) and lipid metabolic regulation while also possessing the capacity to exacerbate inflammation and induce cutaneous scarring. Additionally, recent investigations underscore the therapeutic potential inherent in macrophage modulation and challenge current anti-inflammatory strategies for acne vulgaris. This review distills contemporary advances, specifically examining the dual roles of macrophages, underlying regulatory frameworks, and emergent therapeutic avenues. Such nuanced insights hold the promise of guiding future explorations into the molecular etiology of acne and the development of more efficacious treatment modalities.

Abstract Background Circulating tumor cells (CTCs), an indispensable liquid biopsy classifier, can provide extra information for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Methods We systematically analyzed the peripheral blood of preoperative HCC patients (n = 270) for CTC number, Ki67 index reflecting the proliferative CTC percentage (PCP), and CTC clusters correlated with the characteristics of malignant HCC tumors. Results Driver gene mutations were found with high levels of consistency between CTCs and primary tumors (n = 73). CTC number and PCP were associated with tumor size, microvascular invasion (MVI), presence or absence of multiple tumors, and thrombosis significantly. CTC number and PCP robustly separated patients with and without relapse, with a sensitivity of 88.89%/81.48% and a specificity of 72.73%/94.81% in the training set (n = 104) and corresponding values of 80.00%/86.67% and 78.38%/89.19% in the validation set (n = 52), showing a better performance than that associated with the alpha‐fetoprotein (AFP) level. CTC number, PCP, CTC clusters, and MVI were independent significant risk factors for HCC recurrence (P = 0.0375, P

Objective To investigate the association between HLA-A, B, DRB1 alleles and chronic renal failure (CRF) in Han population of Shandong Peninsula. Methods Sequence specific oligonucleotide probe-polymerase chain reaction (PCR-SSO) was used to genotype 880 patients with CRF in the Han population of Shandong Peninsula. The allele frequencies of HLA-A, B and DRB1 were compared with 865 hematopoietic stem cell voluntary donors, and the association between HLA gene polymorphism and CRF was analyzed. Results A total of 33 HLA-A alleles, 76 HLA-B alleles and 39 HLA-DRB1 alleles were detected in the study group. DRB1*11∶01 (6.70% vs 4.45%) and DRB1*12∶02 (8.69% vs 5.90%) in CRF group were significantly higher than those in the control(Pc

The catalytic performance of metal‒organic frameworks can be tuned by introducing defects in their structure. Here, the authors introduce defects and impregnate ruthenium nanoparticles in cationic metal-organic frameworks, which enables enhanced recyclability and catalytic performance in D-glucose hydrogenation.

Abstract. Rosacea is a chronic inflammatory skin disease that primarily affects the centrofacial areas and mainly manifests as recurrent flushing and erythema. In recent years, there has been progress in the understanding of the diagnosis and treatment of rosacea. Therefore, a group of dermatological experts updated the guidelines based on the 2016 expert consensus statement on rosacea diagnosis and treatment in China. These new guidelines propose diagnostic criteria for rosacea at different sites to further standardize the diagnosis and treatment of rosacea in China.

Bacterial peptidoglycan (PGN) stimulates toll-like receptor 2 (TLR2) on the surface of keratinocytes (KCs), triggering signaling pathways that promote an innate immune response. However, excessive TLR2 activation can lead to inappropriate inflammation, which contributes to skin conditions such as rosacea. To better treat these conditions, there is a need to understand the molecular mechanisms that regulate the cellular response to TLR2 activation in the skin. Aryl hydrocarbon receptor (AhR) is a transcription factor that modulates the immune response in KCs and is a promising therapeutic target for inflammatory skin diseases. Here, we investigated the role of the AhR in regulating the transcriptional response of human KCs to PGN. We performed whole-transcriptome sequencing in wild-type and AhR-depleted KCs after PGN stimulation. AhR depletion altered the expression of 72 genes in response to PGN, leading to increased expression of 48 genes and repression of 24 genes, including interleukin (IL)-1β. Chromatin immunoprecipitation showed that PGN stimulation resulted in AhR binding the promoters of IL-1β and IL-6 to activate them. More broadly, AhR promoted inflammatory gene expression by increasing JNK/mitogen-activated protein kinase signaling and FosB expression. Finally, we observed that AhR depletion increased TLR2 expression itself, raising the hypothesis that AhR may serve to restrain TLR2-mediated inflammation in KCs through negative feedback. Viewed together, our findings demonstrate a significant and complex role for AhR in modulating the expression of inflammatory genes in KCs in response to PGN.

Abstract. Acne inversa/hidradenitis suppurativa is a chronic, recurrent, inflammatory skin disease that affects the pilosebaceous units, causinfollicular occlusion. The etiology and pathogenesis of acne inversa/hidradenitis suppurativa involves internal and external factors such as genetic susceptibility, inflammation and immunity, microorganisms, obesity, and smoking. acne inversa/hidradenitis suppurativa is difficult to treat, and the current aim of treatment is to control the frequency and duration of disease flares and improve the quality of life. Treatment protocols for acne inversa/hidradenitis suppurativa should be selected based on the disease severity grade. Medical treatments include antibiotics, retinoids, biologics, immunosuppressive agents, and antiandrogen agents. Adjuvant treatments include surgery and laser/light therapies. This consensus aims to further standardize the diagnosis and treatment procedures of acne inversa/hidradenitis suppurativa in China to facilitate its diagnosis and treatment.

Sebaceous glands (SGs) originate from hair follicular stem cells and secrete lipids to lubricate the skin. The coordinated effects of intrinsic and extrinsic aging factors generate degradation of SGs at a late age. Senescence of SGs could be a mirror of the late aging of both the human body and skin. The procedure of SG aging goes over an initial SG hyperplasia at light-exposed skin areas to end with SG atrophy, decreased sebum secretion, and altered sebum composition, which is related to skin dryness, lack of brightness, xerosis, roughness, desquamation, and pruritus. During differentiation and aging of SGs, many signaling pathways, such as Wnt/β-catenin, c-Myc, aryl hydrocarbon receptor (AhR), and p53 pathways, are involved. Random processes lead to random cell and DNA damage due to the production of free radicals during the lifespan and neuroendocrine system alterations. Extrinsic factors include sunlight exposure (photoaging), environmental pollution, and cigarette smoking, which can directly activate signaling pathways, such as Wnt/β-catenin, Notch, AhR, and p53 pathways, and are probably associated with the de-differentiation and hyperplasia of SGs, or indirectly activate the abovementioned signaling pathways by elevating the inflammation level. The production of ROS during intrinsic SG aging is less, the signaling pathways are activated slowly and mildly, and sebocytes are still differentiated, yet terminal differentiation is not completed. With extrinsic factors, relevant signaling pathways are activated rapidly and fiercely, thus inhibiting the differentiation of progenitor sebocytes and even inducing the differentiation of progenitor sebocytes into keratinocytes. The management of SG aging is also mentioned.

Colorectal cancer (CRC) is one of the most common malignant tumors. The morbidity and mortality rates have been increasing all over the world. It is critical to elucidate the mechanism of CRC occurrence and development. However, tumor microenvironment (TME) includes immune cells, fibroblasts, endothelial cells, cytokines, chemokines and other components that affect the progression of CRC and patients’ prognosis. Non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) without protein-coding ability have been shown to engage in tumor microenvironment-mediated angiogenesis and metastasis. Therefore, clarifying the mechanism of ncRNAs regulating the microenvironment is very important to develop the therapeutic target of CRC and improve the survival time of patients. This review focuses on the role and mechanism of ncRNAs in the CRC microenvironment and puts forward possible clinical treatment strategies.

RNA binding motif protein 15 (RBM15) is a key regulatory factor involved in N6-methyladenosine (m6A) methylation. It has been reported that RBM15 plays an important role in the progress of laryngeal squamous cell carcinoma (LSCC), promoting LSCC migration and invasion. However, the role of RBM15 in human different cancers remains unknown. This study aims to analyze the prognostic value of RBM15, and to demonstrate the correlation between RBM15 expression and tumor immunity, as well as to provide clues for further mechanism research. The results showed that RBM15 was mutated or copy number varied in 25 types of cancer. RBM15 mRNA was abnormally up-regulated across various cancers. Survival analysis suggested high expression of RBM15 was associated with poor prognosis in many cancer types. Among these, it affected patients’ overall survival (OS) in 10 cancer types, disease-free interval (DFI) in 8 cancer types, progression-free interval (PFI) in 12 cancer types and disease-specific survival (DSS) in 7 cancer types. Importantly, in pancreatic adenocarcinoma (PAAD), overexpression of RBM15 is associated with patients’ OS, DFI, PFI, or DSS. In addition, RBM15 expression was positively correlated with immune infiltrating cells in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and PAAD. Moreover, RBM15 expression showed a strong correlation with immune checkpoint markers in PAAD. Cell counting kit-8 (CCK-8) assay showed that knockdown of RBM15 significantly inhibited the proliferation of pancreatic cancer cells. PPI analysis showed USP10, USP24, SMG1, NRAS were closely connected with RBM15 alterations. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that many biological processes (BP), cellular components (CC), molecular functions (MF), cancer related pathways including “sister chromatid cohesion”, “peptidyl-serine phosphorylation”, “cell division”, “nucleoplasm”, “nucleus”, “protein binding”, “protein serine/threonine kinase activity”, “T cell receptor signaling pathway”, “Cell cycle” were regulated by RBM15 alterations. Taken together, pan-cancer analysis of RBM15 suggested it may be served as a prognostic biomarker and immunotherapeutic target for PAAD.

To analyze and construct a survival-related endogenous RNA (ceRNA) network in gastric cancer (GC) with lymph node metastasis, we obtained expression profiles of long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs) in GC from The Cancer Genome Atlas database. The edgeR package was used to screen differentially expressed lncRNAs, mRNAs, and miRNAs between GC patients with lymphatic metastasis and those without lymphatic metastasis. Then, we used univariate Cox regression analysis to identify survival-related differentially expressed RNAs. In addition, we used multivariate Cox regression analysis to screen lncRNAs, miRNAs, and mRNAs for use in the prognostic prediction models. The results showed that 2,247 lncRNAs, 155 miRNAs, and 1,253 mRNAs were differentially expressed between the two patient groups. Using univariate Cox regression analysis, we found that 395 lncRNAs, eight miRNAs, and 180 mRNAs were significantly related to the survival time of GC patients. We next created a survival-related network consisting of 59 lncRNAs, seven miRNAs, and 36 mRNAs. In addition, we identified eight RNAs associated with prognosis by multivariate Cox regression analysis, comprising three lncRNAs (AC094104.2, AC010457.1, and AC091832.1), two miRNAs (miR-653-5p and miR-3923), and three mRNAs (C5orf46, EPHA8, and HPR); these were used to construct the prognostic prediction models, and their risk scores could be used to assess GC patients’ prognosis. In conclusion, this study provides new insights into ceRNA networks in GC and the screening of prognostic biomarkers for GC.

BackgroundBRCA1-associated protein (BRAP) is a critical gene that regulates inflammation-related signaling pathway and affects patients’ prognosis in esophageal squamous cell carcinoma (ESCC). However, its roles in different cancers remain largely unknown.MethodsBRAP expression in human pan-cancer was analyzed via the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to evaluate the association between BRAP expression with mismatch repair (MMR) gene mutation and DNA methyltransferase. We evaluated the influence of BRAP on clinical prognosis by univariate survival analysis. Moreover, the correlation between BRAP and tumor immune infiltration was analyzed via the Tumor Immune Evaluation Resource (TIMER) database. Pearson correlation analysis was used to investigate the correlation between BRAP expression and immune checkpoint genes expression.ResultsBRAP is abnormally overexpressed and significantly correlated with MMR gene mutation level and DNA methyltransferase expression in human pan-cancer. Univariate survival analysis showed that BRAP was significant with patients’ overall survival (OS) in six cancer types, disease-free interval (DFI) in three cancer types, and progression-free interval (PFI) in two cancer types. Remarkably, increased BRAP expression was strongly correlated with patients’ poor prognosis in liver hepatocellular carcinoma (LIHC), whether OS (P < 0.0001, hazard ratio (HR) = 1.1), DFI (P = 0.00099, HR = 1.06), or PFI (P = 0.00025, HR = 1.07). Moreover, a positive relationship was found between BRAP expression and immune infiltrating cells including B cell, CD4 + T cell, CD8 + T cell, dendritic cell, macrophage cell, and neutrophil cell in colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), and LIHC. Additionally, BRAP expression showed strong correlations with immune checkpoint genes in LIHC.ConclusionBRAP expression is increased in human pan-cancer samples compared with normal tissues. Overexpression of BRAP is correlated with poor prognosis and immune infiltration in multiple cancers, especially in LIHC. These findings suggest that BRAP may be used as a potential molecular biomarker for determining prognosis and immune infiltration in LIHC.

Colorectal cancer (CRC) is one of the most common malignant tumors in China. Fufang Yiliu Yin (FYY) is a traditional Chinese medicine formula used in clinical practice for cancer treatment, but its effectiveness and mechanism of action in human CRC are unclear. In this study, we investigated the antitumor effect of FYY on HCT116 and SW480 human CRC cell lines in vitro and evaluated the underlying molecular mechanism. A subcutaneous xenograft mouse model was used to confirm the antitumor effect in vivo. The components and targets of FYY were collected from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. CRC targets were collected via the GeneCards and OMIM databases. Protein–protein interactions were explored using the STRING platform. Cytoscape was used to construct drug–disease–target networks. KEGG and GO analyses were performed to investigate common FYY and CRC targets. FYY significantly inhibited cell proliferation and induced HCT116 and SW480 cell apoptosis. Cell proliferation was blocked at the G0/G1 phase, while cell apoptosis was promoted at the early stage. According to the network pharmacological analysis, quercetin and kaempferol were the most bioactive compounds of FYY. The key targets of FYY were cyclin-D1, MAPK8, and EGFR. GO analysis showed that core targets included the apoptotic signaling pathway, response to steroid hormone, and cellular response to organic cyclic compound. The KEGG pathway analysis showed that FYY may affect CRC through the PI3K/Akt pathway. In vitro, FYY significantly inhibited tumor growth. Pathway analysis confirmed that FYY induced cell apoptosis by modulating PI3K/Akt signaling and BCL-2 family proteins. Hence, our findings indicate that FYY may be a promising adjuvant therapy for CRC.

Abstract Background In vitro studies showed that the aryl hydrocarbon receptor (AHR) contributed to the development of cutaneous squamous cell carcinomas, but supporting clinical data are lacking. Methods Immunohistochemical analysis was used to detect the expression of AHR, CYP1A1, EGFR, and Ki-67 in 10 actinic keratosis (AK) cases, 10 Bowen disease (BD) cases, 20 cutaneous squamous cell carcinoma (cSCC) cases and 20 normal skin samples. H-scores were used to assess the immunoreactivity. Results Weak positive AHR immunoreactivity was found in all normal skin samples, while strong positive AHR immunoreactivity was found in atypical squamous proliferation (AK, BD and cSCC) cases. H-scores and the rate of strong immunostaining of the atypical squamous proliferation cases were higher than those of normal controls (p 0.05). The H-score of AHR was positively correlated with EGFR expression (r = 0.54, p

Chloracne is the most sensitive and specific marker for a possible dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) intoxication. It is clinically characterized by multiple acneiform comedone-like cystic eruptions mainly involving face in the malar, temporal, mandibular, auricular/retroauricular regions, and the genitalia, often occurring in age groups not typical for acne vulgaris. Histopathology is essential for a definite diagnosis, which exhibits atrophy or absence of sebaceous glands as well as infundibular dilatation or cystic formation of hair follicles, hyperplasia of epidermis, and hyperpigmentation of stratum corneum. The appearance of chloracne and its clinical severity does not correlate with the blood levels of dioxins. Pathogenesis of chloracne remains largely unclear. An “aryl hydrocarbon receptor”-mediated signaling pathway affecting the multipotent stem cells in the pilosebaceous units is probably the major molecular mechanism inducing chloracne. Chloracne is resistant to all the available treatment modalities used to treat acne. The aim of treatment is to lower or to eliminate the accumulated dioxins in the body at the very beginning of intoxication, e.g., by using dioxin-chelating substances such as synthetic dietary fat substitutes. The problem of dioxin contamination and its potential health hazards should be taken seriously in the wave of industrial globalization in the twenty-first century. Clinicians, especially dermatologists, are in the forefront of early diagnosis of dioxin intoxication.