Membranous aplasia cutis congenita: A rare case report highlighting clinical presentation, genetic insights, and the need for comprehensive evaluation.

Introduction: Membranous aplasia cutis congenita (MACC) is the most common clinical subtype of aplasia cutis congenita (ACC). It is typified by a localized skin lesion devoid of hair and features a membranous surface. While most MACC individuals do not present with concurrent abnormalities, it can sometimes co-occur with additional physical anomalies and various malformation syndromes. Moreover, the underlying causes of MACC remain elusive. Case presentation: We describe a case of a 6-month-old female infant diagnosed with MACC. The patient presented with a midline skin lesion on the occipital scalp, characterized by a glistening surface and a hair collar sign. Dermoscopic examination revealed specific features, including translucency, telangiectasia, and hypertrichosis. The infant had a history of patent foramen ovale, and further examination uncovered an asymptomatic ventricular septal defect. Whole exome sequencing revealed 20 gene variants relevant to the clinical phenotype of the patient, suggesting a possible association with MACC. Conclusion: MACC is a rare and underreported condition, primarily diagnosed based on its distinctive clinical features. It is imperative to emphasize the significance of thorough evaluations in MACC patients, encompassing developmental, cardiac, neurological, and genetic assessments to facilitate early detection and the exclusion of potentially life-threatening comorbidities. Importantly, genetic characterization, as demonstrated in this case, contributes to our understanding of MACC's etiology and highlights the need for further research in this field.

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management.

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.

Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

A Case Report and Literature Review of Bilateral Cervical Chondrocutaneous Branchial Remnants.

Chondrocutaneous branchial remnants (CCBRs) are rare congenital heterotopic tissue formations originating from the first or second embryonic branchial arches. Clinically, CCBRs are characterized predominantly by unilateral and solitary cartilaginous nodules found on the lower neck region. Herein, we present a case of CCBRs in a 9-year-old male patient who presented with horn-shaped projecting masses on either side of the anterior border of the sternocleidomastoid muscle. The pathological report following surgical resection revealed that the lesion was located in the dermis and consisted primarily of hyaline cartilage tissue enclosed by a fibrous capsule, with few local vascular proliferations. Based on the clinical and pathological features, the patient was ultimately diagnosed with congenital bilateral cervical chondrocutaneous branchial remnants.

Mitochondrial DNA depletion causes decreased ROS production and resistance to apoptosis.

Mitochondrial DNA (mtDNA) depletion occurs frequently in many diseases including cancer. The present study was designed in order to examine the hypothesis that mtDNA­depleted cells are resistant to apoptosis and to explore the possible mechanisms responsible for this effect. Parental human osteosarcoma 143B cells and mtDNA­deficient (Rho˚ or ρ˚) 206 cells (derived from 143B cells) were exposed to different doses of solar-simulated ultraviolet (UV) radiation. The effects of solar irradiation on cell morphology were observed under both light and fluorescence microscopes. Furthermore, apoptosis, mitochondrial membrane potential (MMP) disruption and reactive oxygen species (ROS) production were detected and measured by flow cytometry. In both cell lines, apoptosis and ROS production were clearly increased, whereas MMP was slightly decreased. However, apoptosis and ROS production were reduced in the Rho˚206 cells compared with the 143B cells. We also performed western blot analysis and demonstrated the increased release of cytosolic Cyt c from mitochondria in the 143B cells compared with that in the Rho˚206 cells. Thus, we concluded that Rho˚206 cells exhibit more resistance to solar­simulated UV radiation­induced apoptosis at certain doses than 143B cells and this is possibly due to decreased ROS production.

Luteolin decreases the UVA­induced autophagy of human skin fibroblasts by scavenging ROS.

Luteolin (LUT) is a flavone, which is universally present as a constituent of traditional Chinese herbs, and certain vegetables and spices, and has been demonstrated to exhibit potent radical scavenging and cytoprotective properties. Although LUT has various beneficial effects on health, the effects of LUT on the protection of skin remain to be fully elucidated. The present study investigated whether LUT can protect human skin fibroblasts (HSFs) from ultraviolet (UV) A irradiation. It was found that, following exposure to different doses of UVA irradiation, the HSFs exhibited autophagy, as observed by fluorescence and transmission electron microscopy, and reactive oxygen species (ROS) bursts, analyzed by flow cytometry, to differing degrees. Following incubation with micromolar concentrations of LUT, ROS production decreased and autophagy gradually declined. In addition, the expression of hypoxia­inducible factor­1α and the classical autophagy­associated proteins, LC3 and Beclin 1 were observed by western blotting. Western blot analysis showed that the expression levels of HIF­1α, LC3­II and Beclin 1 gradually decreased in the UVA­irradiated HSFs following treatment with LUT. These data indicated that UVA­induced autophagy was mediated by ROS, suggesting the possibility of resistance against UV by certain natural antioxidants, including LUT.

Enforced expression of microRNA-21 influences the replication of varicella-zoster virus by triggering signal transducer and activator of transcription 3.

Varicella-zoster virus (VZV) causes chronic pain and serious complications, including zoster paresis. However, the mechanism of VZV replication, a critical part of VZV pathogenesis, remains largely unknown and was investigated in the present study. The upregulation of microRNA-21 (miR-21) was identified following VZV infection in vitro by quantitative polymerase chain reaction. The hypothesis that the overexpression of miR-21 activates the signal transducer and activator of transcription 3 (STAT3) signaling pathway was validated by measuring the mRNA expression levels of STAT3 and the anti-apoptotic protein survivin in human malignant melanoma (MeWo) and human embryonic lung fibroblast (HELF) cell lines transfected with miR-21-mimic and comparing them with those in cells transfected with miR-control. To further study the interaction of miR-21, STAT3 and VZV replication, the effects of miR-21 overexpression and STAT3 knockdown were evaluated. Higher virus titers were detected when miR-21 was upregulated in vitro. Moreover, it was identified that significantly lower virus titers were present in MeWo cells in which STAT3 was knocked down. In addition, the overexpression of miR-21 did not stimulate VZV replication in the MeWo cell line when the STAT3 gene was silenced. Therefore, the observations of the present study indicate that the enforced expression of miR-21 promotes the replication of VZV by activating STAT3 in vitro.

Cytotoxic triterpene saponins from Clematis mandshurica.

Two new triterpene saponins, mandshunosides A and B (1 and 2), were isolated from the roots and rhizomes of Clematis mandshurica. Their structures were elucidated on the basis of spectroscopic evidence and hydrolysis products. Compounds 1 and 2 showed inhibitory activities against two colorectal human cancer cells HCT 116 (IC50 2.1 µM for 1 and 2.5 µM for 2) and HT-29 (IC50 3.7 µM for 1 and 3.3 µM for 2).

Stepwise identification of HLA-A*0201-restricted CD8+ T-cell epitope peptides from herpes simplex virus type 1 genome boosted by a StepRank scheme.

Identification of immunodominant epitopes is the first step in the rational design of peptide vaccines aimed at T-cell immunity. To date, however, it is yet a great challenge for accurately predicting the potent epitope peptides from a pool of large-scale candidates with an efficient manner. In this study, a method that we named StepRank has been developed for the reliable and rapid prediction of binding capabilities/affinities between proteins and genome-wide peptides. In this procedure, instead of single strategy used in most traditional epitope identification algorithms, four steps with different purposes and thus different computational demands are employed in turn to screen the large-scale peptide candidates that are normally generated from, for example, pathogenic genome. The steps 1 and 2 aim at qualitative exclusion of typical nonbinders by using empirical rule and linear statistical approach, while the steps 3 and 4 focus on quantitative examination and prediction of the interaction energy profile and binding affinity of peptide to target protein via quantitative structure-activity relationship (QSAR) and structure-based free energy analysis. We exemplify this method through its application to binding predictions of the peptide segments derived from the 76 known open-reading frames (ORFs) of herpes simplex virus type 1 (HSV-1) genome with or without affinity to human major histocompatibility complex class I (MHC I) molecule HLA-A*0201, and find that the predictive results are well compatible with the classical anchor residue theory and perfectly match for the extended motif pattern of MHC I-binding peptides. The putative epitopes are further confirmed by comparisons with 11 experimentally measured HLA-A*0201-restrcited peptides from the HSV-1 glycoproteins D and K. We expect that this well-designed scheme can be applied in the computational screening of other viral genomes as well.

Large scale analysis of genes contributing to the herbal preparation dependent hippocampal plasticity in postischemic rehabilitation.

Herbal preparations can affect the expression of many genes involved in the ischemic process. These genes have been providing insights into the molecular basis of brain plasticity in stroke rehabilitation. However, the extent of plasticity has not been investigated using a chemogenomic approach. A herbal preparation (270 mg/kg) used to treat ischemic mice for 45 days after global ischemia resulted in a significant decrease in infarct volume and neurological score compared with that of vehicle. This effect was characterized by investigating chemical genomic profiles of the mouse hippocampus with a cDNA microarray containing 1176 known genes. Treatment with the herbal preparation reversed the expression of 46 genes out of 100 genes altered in untreated ischemic mouse hippocampus. These data indicated that more genes were upregulated (60.78%) than downregulated (30.61%), and only 46 genes (46%) appear to be prime targets for therapeutic intervention in ischemia. The altered genes can be classified into seven groups, including signal transduction (12 genes, 27%), oncogene (8 genes, 17%), and transcriptional regulation (7 genes, 15%). Such multiple plasticity of expression could be considered as the beneficial role of this herbal preparation in stroke rehabilitation. Changes in gene expression of nuclear factor of activated T cells, 14-3-3 eta, and beta-arrestin suggest a potential role for the immune system in this plasticity. Brain plasticity originates from a balance of up and downregulated genes (Yin and Yang), and reversal of gene expression in multiple pathways indicates that a complex signaling network may be constructed and investigated further.

[Determination of citrinin in red kojic by HPCE].

OBJECTIVE: To establish an instant determination method of citrinin in red kojic by high performance capillary electrophorphores for the first time. METHOD: Red kojic was extracted with the mixtrue of Toluene and ethyl acetate (70:30). Separation was carried out in an uncoated fused silica capillary (50 microm x 45.0 cm). Meanwhile, a running voltage 15 kV, 20 mmol L(-1) borax buffer with 10.0 mmol L(-1) sodium deoxycholate (pH 9.3) and a UV detector at 212 nm were adopted. RESULT: Regression equation of citrinin was Y=9434 + 16781X (r =0.990), The lower limit of quantification (S/N > or =3) was 0.5 mg mL(-1). The assay coefficients of variation ranged from 98.8% to 101.1%. The intra and inter recovery ranged from 0.83 to 1.54% and from 1.86 to 5.09%. Twenty samples were determined with the method. CONCLUSION: The method is proved to be simple, rapid and accurate, and it can be used to determine citrinin in red kojic.

Dioscorea opposita reverses dexamethasone induced insulin resistance.

The effects of Dioscorea opposita (huai shan yao, HSY) on dexamethasone-induced insulin resistance were investigated in vitro and in vivo. D. opposita extract reduced significantly the blood insulin and glucose levels in dexamethasone-induced diabetic rats. In vitro, HSY significantly enhanced insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Moreover, HSY increase the mRNA expression of GLUT4 glucose transporter in 3T3-L1 adipocytes. These data suggest that D. opposita has insulin sensitivity that is associated with the regulation of GLUT4 expression.

[The experiment study on RNAi inhibiting the expression of survivin and inducing the apoptosis of pancreatic cancer cells].

OBJECTIVE: To investigate the inhibitory effects of RNAi expression vector suppressing the expression of survivin and inducing the apoptosis of pancreatic cancer cell PANC-1. METHODS: The expression of survivin was examined with RT-PCR and immunofluorescence protocols. The survivin gene was cloned into the T-vector and sequenced, at the same time, the RNAi expression vectors aimed survivin were successfully constructed, and then transfected into PANC-1 cells with liposomes. The expression of survivin mRNA was detected with RT-PCR and Western-blot techniques. The rate of cell apoptosis was measured with FACS. RESULTS: There was a high degree expression of survivin in PANC-1 cells. The DNA sequence was according with the survivin gene in GENE BANK. The survivin expression was inhibited about 70% by pTZU6 + 1-svv2 RNAi expression vectors, and the apoptosis cells increased. CONCLUSION: The RNAi expression vector can effectively inhibit the survivin expression and induce the apoptosis in PANC-1 cells.

[Synthesis of phenyloxyisobutyric acid derivatives and their antidiabetic activity in vitro].

AIM: To design and synthesize new phenyloxyisobutyric acid analogues as antidiabetic compounds. METHODS: Eight new target compounds were synthesized by combination of lipophilic moieties and acidic moiety with nucleophilic replacement or Mitsunobu condensation. The eight compounds were confirmed by 1H NMR, 13C NMR, IR and MS. RESULTS: In vitro insulin-sensitizing activity (3T3-L1 adipocyte) demonstrated, that the cultured glucose concentration of up-clear solution detected with GOD-POD assay were 5.942, 6.339, 6.226 and 6.512 mmol x L(-1), respectively, when rosiglitazone, pioglitazone, compounds A and B were added to the insulin-resistant system. CONCLUSION: In vitro insulin-sensitizing activity of target compound A is in between that of rosiglitazone and pioglitazone, and activity of target compound B is slightly less than that of pioglitazone.

[Dissipation mechanism of excessive energy in umbilical orange under phosphorus deficiency and strong light stress].

The dissipation mechanism of excessive energy of umbilical orange under phosphorus deficiency and strong light stress was studied with solution culture method. The results showed that under phosphorus deficiency and strong light stress, the photosynthetic pigment content, net photosynthetic rate (Pn), photorespiration rate (Pr), maximum fluorescence (Fm), photochemical efficiency (Fv/Fm) and electron transmit rate (ETR) of umbilical orange were all declined, while original fluorescence (Fo) and Pr/Pn ratio were raised. The fast-phase (qNf) of non-photochemical quenching of chlorophyll fluorescence was decreased, while the middle-phase (qNm) and slow-phase (qNs) were increased. After treated with DTT, Fo turned higher, but qNm and qNs were much lower than the control (H2O), while qNf did not have any significant change. Phosphorus deficiency and strong light stress aggravated photoinhibition of photosynthesis, which in turn started up several dissipation mechanisms in umbilical orange leaf.

[Design, synthesis and insulin-sensitizing activity of some peroxisome proliferator-activated gamma agonists].

AIM: To find new peroxisome proliferator-activated y agonists with high activity and low toxicity. METHODS: Based on JTT-501 and JTT-20993, new isoxazolidine-3,5-dione and noncyclic 1,3-dicarbonyl compounds were designed and synthesized. Their insulin-sensitizing activities were evaluated. RESULTS: Eight new compounds were obtained. The structures of synthesized compounds were characterized by NMR, MS and IR. Four compounds (1A-4A) showed insulin-sensitizing activities. CONCLUSION: Compounds (1A and 3A) showed excellent insulin-sensitizing activities and should be worth further investigation.

Microarray analysis of gene expression on herbal glycoside recipes improving deficient ability of spatial learning memory in ischemic mice.

In order to reveal the mechanism of herbal glycoside recipes retrieving deficient ability of spatial learning memory in mice suffering from cerebral ischemia/reperfusion, a microarray system was used to analyze gene expression in those groups with increasing ability of spatial learning memory who were different from ischemic mice. In this work, we reported a comprehensive characterization of gene expression profiles of mouse hippocampus by the use of cDNA microarray system containing 1176 known genes in middle cerebral artery occlusion (MCAO) ischemic mice after treating with different dosage recipes of glycoside herbs (30, 90, and 270 mg/kg). The ability of spatial learning memory in ischemic mice was found to be decreased. The pathological process in ischemic mouse brain showed that a complex related to 100 genes' expression yielded 1.8-fold. Dose-dependent effects showed an improvement in the deficient ability and reduction in infarct volume when treated with glycoside recipes. Many genes (38-46) in expression were found greater than 1.8-fold in those effective recipes groups, including genes in cell cycle regulation, signal transduction, nerve system transcription factors, DNA binding protein, etc. Nine genes related to retrieving deficient ability of spatial learning memory treated with glycoside recipes were also found in this study. These results suggest that microarray analysis of gene expression might be useful for elucidating the mechanisms of pharmacological function of recipes.

[Study on point mutations in mitochondrial DNA control region for replication DLP(6) of cultured dermal fibroblast with 8-MOP/UVA treatment].

OBJECTIVE: To investigate the relationships between skin photoaging and point mutations in mitochondrial DNA (mtDNA) control region for replication of dermal fibroblast. METHODS: Cultured dermal fibroblasts were treated by 8-methoxypsora len /ultraviolet A (8-MOP/UVA). mtDNA was extracted by one-step-method and th e PCR products of D-loop and adjacent transcription promoter (DLP(6)) fragment of mtDNA control region for replication were detected by polymerase chain reaction-single strain conformation polymorphism and direct sequencing. RESULTS: After treated by 8-MOP/UVA, point mutations of 414 T-->G of DLP(6) fragment of mtDNA control region for replication largely accumulated. CONCLUSION: Accumulation of point mutations of DLP(6) fragment of mtDNA control region for replication may be closely associated with skin photoaging.