Malus toringoides (Rehd.) Hughes decoction alleviates ISO-induced cardiac fibrosis by inhibiting cardiomyocyte inflammation and pyroptosis via the HK1/NLRP3-signaling pathway.

Malus toringoides (Rehd.) Hughes leave, called "Eseye (Ese)", is a traditional medicinal plant from the Tibet province of China that has efficiency of anti-inflammatory, antioxidant and anti-apoptosis to treat cardiac conditions. We herein explored the underlying protective mechanisms of Ese decoction in isoproterenol (ISO)-induced cardiac fibrosis (CF). And treatment with an Ese decoction attenuated tissue injury and decreased the release of IL-1ß, IL-18, TNF-α, and caspase-3 and elevated the Bax/Bcl-2 ratio in CF mice. Damage to the mitochondrial ultrastructure of myocardium was alleviated, and the level of ROS was markedly diminished with Ese treatment. Ese inhibited the expression of proteins associated with pyroptosis by the HK1/NLRP3-signaling pathway, and also improved CF. Based on anti-inflammatory, antioxidative and anti-apoptosis activities effects of Ese decoction, we found that Ese protected against ISO-induced CF, which attributed to its inhibition of inflammation and pyroptosis as mediated by the HK1/NLRP3-signaling pathway.

Compound heterozygous ABCA12 variants identified in a Chinese patient with congenital ichthyosiform erythroderma: Advancing genotype-phenotype correlations and literature review.

BACKGROUND: Ichthyosis is a common keratotic skin disease with high clinical, etiological and genetic heterogeneity. There are four types of non-syndromic hereditary ichthyoses, among which autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of recessive Mendelian disorders. ARCI present with different phenotypes and ABCA12 pathogenic variants have been shown to cause complex ARCI phenotypes, including harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). METHODS: A sporadic male patient, clinically diagnosed with CIE, was enrolled in this study. Exome sequencing was combined with Sanger sequencing to confirm the diagnosis and identify the pathogenic variants. In silico predictions were made using multiple software programs, and the identified variants were interpreted using the ACMG guidelines. A review of all literature reported ABCA12 variants was performed to explore genotype-phenotype correlations. RESULTS: Compound heterozygous ABCA12 variants [c.5381+1G>A and c.5485G>C (p.Asp1829His)] (NM_173076) were identified. The two variants were not detected in the public database. c.5381+1G>A is predicted to affect ABCA12 mRNA splicing and Asp1829 is highly conserved among various species. In silico analysis suggested that these two variants were responsible for the phenotype of the patient. Genotype-phenotype correlation analysis showed that biallelic truncation variants and/or exon/amino acid deletions in ABCA12 are the most common causes of HI. Biallelic missense variants are most common in LI and CIE. CONCLUSIONS: The compound heterozygous ABCA12 variants caused the CIE phenotype observed in the patient. The spectrum of ABCA12 pathogenic variants were broaden. Genotype-phenotype correlation analysis provided detailed evidence which can be used in future prenatal diagnosis and can inform the need for genetic counselling for patients with ABCA12-related ARCIs.

Cichoric acid improves isoproterenol-induced myocardial fibrosis via inhibition of HK1/NLRP3 inflammasome-mediated signaling pathways by reducing oxidative stress, inflammation, and apoptosis.

Cichoric acid (CA), a natural phenolic compound found in many plants, has been reported to have antioxidant, anti-inflammatory, hypoglycemic, and other effects. The aim of this study was to determine the potential role and underlying mechanisms of CA in isoproterenol (ISO)-induced myocardial fibrosis (MF). The MF model was induced by subcutaneous ISO injection in mice. Blood and heart tissue were collected for examination. Hematoxylin and eosin staining and Masson's trichrome staining were used to evaluate the histopathological changes and collagen deposition. The production of reactive oxygen species markers was observed by fluorescence microscopy, the degree of cardiomyocyte microstructure injury was observed by transmission electron microscope, and oxidative stress factors were detected by kit method, and the effect of CA on inflammatory factors was detected by ELISA. The expression levels of collagen proteins and signaling pathways were further investigated by western blotting. The results showed that CA inhibited the expression of ISO-induced proinflammatory factors (TNF-α, IL-1ß, and IL-18) and proteins (HK1, NLRP3, caspase-1, cleaved-caspase-1, and ASC), and regulated the expression of apoptotic factors (caspase-3, cleaved-caspase-3, Bax, and Bcl-2). The results indicated that CA may regulate the HK1/NLRP3 inflammasome pathway by inhibiting HK1 expression and play a protective role in MF.

DNA barcoding identification of grafted Semen Ziziphi Spinosae and transcriptome study of wild Semen Ziziphi Spinosae.

Semen Ziziphi Spinosae (SZS) is the dried and ripe seeds of Ziziphus jujuba var. spinosa. Currently, the yield of naturally grown SZS is unstable owing to environmental factors. Grafting high-quality sour jujube scions onto sour jujube or jujube tree stocks can result in a greater yield. However, the effects of grafting on the quality and gene expression of SZS have rarely been reported. This study used a DNA barcoding technique, high-performance liquid phase-evaporative luminescence detector (HPLC-ELSD), and transcriptomics to investigate the origin and genetic differences between grafted and wild jujube seeds. DNA barcoding identified all samples as Ziziphus jujuba var. spinosa. HPLC-ELSD analysis revealed a higher content of grafted SZS compared to that of the wild SZS. Transcriptome analysis of the metabolic pathways in SZS showed that 22 and 19 differentially expressed gene sequences encoded enzymes related to flavonoids and saponin synthesis, respectively. Weighted correlation network analysis (WGCNA) identified 15 core genes governing the differences in medicinal components between grafted and wild SZS. This study demonstrated the use of DNA barcoding and fingerprint methods to identify jujube seed species and effectively capture ingredient information of medicinal materials. Additionally, transcriptome technology provided data for identifying core differential genes, facilitating studies on quality differences between grafted and wild SZS.

Phlorizin ameliorates myocardial fibrosis by inhibiting pyroptosis through restraining HK1-mediated NLRP3 inflammasome activation.

The specific role of phlorizin (PHL), which has antioxidant, anti-inflammatory, hypoglycemic, antiarrhythmic and antiaging effects, on myocardial fibrosis (MF) and the related pharmacological mechanisms remain unknown. The objective of this study was to determine the protective actions of PHL on isoprenaline (ISO)-induced MF and its molecular mechanisms in mice. PHL was administered at 100 and 200 mg/kg for 15 consecutive days with a subcutaneous injection of ISO (10 mg/kg). MF was induced by ISO and alleviated by treatment with PHL, as shown by reduced fibrin accumulation in the myocardial interstitium and decreased levels of myocardial enzymes, such as creatinine kinase-MB, lactate dehydrogenase, and aspartate transaminase. In addition, PHL significantly decreased the expression of the fibrosis-related factors alpha smooth muscle actin, collagen I, and collagen III induced by ISO. The generation of intracellular reactive oxygen species induced by ISO was attenuated after PHL treatment. The malondialdehyde level was reduced, whereas the levels of superoxide dismutase, catalase, and glutathione were elevated with PHL administration. Moreover, compared to ISO, the level of Bcl-2 was increased and the level of Bax protein was decreased in the PHL groups. PHL relieved elevated TNF-α, IL-1ß, and IL-18 levels as well as cardiac mitochondrial damage resulting from ISO. Further studies showed that PHL downregulated the high expression of hexokinase 1 (HK1), NLRP3, ASC, Caspase-1, and GSDMD-N caused by ISO. In conclusion, our findings suggest that PHL protects against ISO-induced MF due to its antioxidant, anti-apoptotic, and anti-inflammatory activities and via inhibition of pyroptosis mediated by the HK1/NLRP3 signaling pathway in vivo.

X-Linked Reticulate Pigmentary Disorder.

This case report describes a child with generalized reticulate hyperpigmentation and recurrent pneumonia, hypohidrosis, photophobia, and diarrhea.

Si-Ni-San Reduces Hepatic Lipid Deposition in Rats with Metabolic Associated Fatty Liver Disease by AMPK/SIRT1 Pathway.

Background: Metabolic associated fatty liver disease (MAFLD) is a chronic disease characterized by excessive lipid deposition in the liver without alcohol or other clear liver-damaging factors. AMP-activated protein kinase (AMPK)/silencing information regulator (SIRT)1 signaling pathway plays an important role in MAFLD development. Si-Ni-San (SNS), a traditional Chinese medicine, has shown reducing hepatic lipid deposition in MAFLD rats, however, the underlying mechanisms of SNS are barely understood. Purpose: The aim of this research was to investigate the mechanisms of SNS in reducing hepatic lipid deposition in MAFLD rats by regulating AMPK/SIRT1 signaling pathways. Methods: The components of SNS were determined by high performance liquid chromatography with mass spectrometry (HPLC-MS) analysis. MAFLD rats were induced by high-fat and high-cholesterol diet (HFHCD), and treated by SNS. SNS-containing serum and Compound C (AMPK inhibitor) were used to treat palmitic acid (PA)-induced HepG2 cells. To elucidate the potential mechanism, lipid synthesis-related proteins (SREBP-1c and FAS), fatty acid oxidation (PPARα and CPT-1), and AMPK/SIRT1 signaling pathway (p-AMPK and SIRT1) were assessed by Western blot. Results: SNS improved serum lipid levels, liver function and reduced hepatic lipid deposition in MAFLD rats. SNS-containing serum reduced lipid deposition in PA-induced HepG2 cells. SNS could up-regulate protein expressions of PPARα, CPT-1, p-AMPK and SIRT1, and down-regulate protein expressions of SREBP-1c and FAS. Similar effects of SNS-containing serum were observed in PA-induced HepG2 cells. Meanwhile, Compound C weakened the therapeutic effects of SNS-containing serum on lipid deposition. Conclusion: SNS could reduce hepatic lipid deposition by inhibiting lipid synthesis and promoting fatty acid oxidation, which might be related with activating the AMPK/SIRT1 signaling pathway. This study could provide a theoretical basis for the clinical use of SNS to treat MAFLD.

Video education improves patients' knowledge and satisfaction in treatment of solar lentigines with picosecond 755-nm alexandrite laser: A retrospective study.

Background: Picosecond lasers are widely used in dermatologic and cosmetic practice. In clinical practice, informed consent for laser treatments is critical to ensure patients' understanding of health information. Objectives: To evaluate whether video-based informed consent improves patient comprehension and satisfaction. Methods: The study was performed from August 1 to November 30, 2022. Solar lentigines patients who fulfilled the inclusion criteria were included. Before October 1, 2022, traditional informed consent methods were performed. In the subsequent 2 months, a video-based informed consent was used as an adjunct to traditional consenting methods. Finally, patient comprehension of relevant knowledge about laser treatment and client satisfaction were assessed. Results: A total of 106 patients were included. The mean number of correct answers in the comprehension assessment in the video-based informed consent group was significantly higher than that in the traditional informed consent group (4.4 ± 1.2 vs. 3.4 ± 1.1, p < 0.001). Compared to the traditional informed consent group, more correct answers in the video-based informed consent group were provided by older patients (3.9 ± 1.2 vs. 2.9 ± 1.1, p = 0.004) and patients with lower education levels (4.1 ± 1.1 vs. 3.0 ± 1.2, p < 0.001). The mean satisfaction score in the video-based informed consent group was significantly higher than that in the traditional informed consent (27.8 ± 5.7 vs. 24.3 ± 6.2, p = 0.003). Conclusion: Video-based informed consent helps patients learn clinical literacy more effectively and improves patient satisfaction, especially in those with lower education levels and older ages.

Application of omics technology to investigate the mechanism underlying the role of San Hua Tang in regulating microglia polarization and blood-brain barrier protection following ischemic stroke.

ETHNOPHARMACOLOGY RELEVANCE: San Hua Tang (SHT) was first mentioned in the book "The Collection of Plain Questions about Pathogenesis, Qi, and Life." SHT has the effect of dispelling wind and dredging collaterals, dredging viscera, and guiding stagnation, and is used in the treatment of ischemic stroke (IS). SHT is composed of Rheum palmatum L., Magnolia officinalis Rehder & E.H.Wilson, Citrus assamensis S.Dutta & S.C.Bhattacharya, and Notopterygium tenuifolium M.L.Sheh & F.T.Pu, which is the traditional prescription of the Tongxia method for the treatment of stroke. Tongxia is one of the "eight methods" used in traditional Chinese medicine, which plays a role in treating diseases by promoting gastrointestinal peristalsis and defecation. Studies have demonstrated a close relationship between gut microbiota metabolism and cerebral stroke; however, the role of SHT in IS treatment through gut microbiota or intestinal metabolites is unclear. AIM OF THE STUDY: To explore the connotation of the Xuanfu theory and clarify the mechanism underlying SHT-mediated opening Xuanfu methods. Through metabolomics, 16S rRNA gene sequencing, and molecular biology techniques, research on the changes in the gut microbiota and blood-brain barrier (BBB) will highlight greater strategies for the treatment of stroke. MATERIALS AND METHODS: We used pseudo-germ-free (PGF) rats combined with an ischemia/reperfusion (I/R) rat model for the follow-up experimental research. PGF rats were prepared by the intragastric administration of an antibiotic cocktail for 6 days, following which SHT was administered for 5 consecutive days. The I/R model was performed 1 day following the concluding administration of SHT. We detected the neurological deficit score, cerebral infarct volume, serum inflammatory factor levels (interleukin IL-6, IL-10, IL-17, and tumor necrosis factor alpha), tight junction-related proteins (Zonula occludens-1, Occludin, and Claudin-5), and small glue plasma cell-associated proteins (Cluster of Differentiation 16/Cluster of Differentiation 206, Matrix metalloproteinase, ionized calcium-binding adapter molecule 1, and C-X3-C Motif Chemokine Ligand 1) 24 h following I/R. Using 16S rRNA gene sequencing and non-targeted metabolomics analysis, we explored the relationship between fecal microecology and serum metabolites. Eventually, we analyzed the correlation between the gut microbiota and plasma metabolic profile as well as the mechanism underlying the SHT-mediated regulation of gut microbiota to protect the BBB following stroke. RESULTS: In IS treatment, SHT is principally involved in reducing neurological injury and the volume of cerebral infarction; protecting the intestinal mucosal barrier; increasing the levels of acetic acid, butyric acid, and propionic acid; promoting the transformation of microglia to the M2 state; reducing inflammatory reactions; and enhancing tight junctions. These therapeutic effects were not observed in the group treated with antibiotics alone or that treated with SHT in combination with antibiotics, thereby indicating SHT plays a therapeutic role through the gut microbiota. CONCLUSION: SHT regulates the gut microbiota, inhibits pro-inflammatory factors in rats with IS, alleviates an inflammatory injury of the BBB, and plays a protective role in the brain.

Multiple Erythematous-Violaceous Patches and Plaques on the Left Upper Arm and Left Side of the Chest.

A woman in her late 20s had multiple, slowly growing, infiltrated erythematous-violaceous patches and plaques with occasional slight pain extending from her left upper arm to the left side of her chest. What is your diagnosis?

Recent Advances of N-2,2,2-Trifluoroethylisatin Ketimines in Organic Synthesis.

The special properties of fluorine atoms and fluorine-containing groups have led to an increasing number of applications for fluorine-containing organic compounds, which are also extremely widely used in the field of new drug development. Unfortunately, naturally fluorinated organics are rare in nature, so the selective introduction of fluorine atoms or fluorine-containing groups into organic molecules is very important for pharmaceutical/synthetic chemists. N-2,2,2-trifluoroethylisatin ketimines have received the attention of many chemists since they were first developed as fluorine-containing synthons in 2015. This paper reviews the organic synthesis reactions in which trifluoroethyl isatin ketimine has been involved in recent years, focusing on the types of reactions and the stereoselectivity of products, and also provides a prospect of its application in this field.

Genetic and phenotypic heterogeneity of multiple lentigines and precise diagnosis in four Chinese families with multiple lentigines.

Lentigines are well-defined, small, brown macules resulting from the accumulation of melanin content in the basement membrane zone with an increase in the number of melanocytes. Hereditary multiple lentigines (ML) can be associated with multiple genes and are not commonly encountered in clinical practice. Patients can solely have skin involvement or present with multisystemic deformative phenotypes. This study aimed to describe four unrelated Chinese families presenting with ML as their first visit symptom. We performed whole-exome sequencing (WES) and Sanger sequencing on all patients and immediate family members for precise molecular diagnosis. Two novel variants c.1548 T > A (p.Ser516Arg) and c.1811C > A (p.Thr604Lys) in SASH1, and two recurrent variants c.1403C > T (p.Thr468Met) and c.1493G > T (p.Arg498Leu) in PTPN11, were identified in these four families. We also summarized the genes associated with ML and differential diagnosis of pigment abnormality. We suggested that the molecular diagnosis of ML should be emphasized because it can help in the clinical differential diagnosis and further genetic counseling and prognosis.