Ganoderic acid D attenuates gemcitabine resistance of triple-negative breast cancer cells by inhibiting glycolysis via HIF-1α destabilization.

BACKGROUND: Gemcitabine (GEM) resistance is the primary reason why combination chemotherapy is limited in triple-negative breast cancer (TNBC). Ganoderic acid D (GAD), a natural triterpenoid compound obtained from Ganoderma lucidum, has been shown to have antitumor activities. However, whether GAD can reverse GEM resistance in TNBC requires further investigation. PURPOSE: This study investigated whether and how GAD could reverse GEM resistance in TNBC as an antitumor adjuvant. METHODS: The effects of GAD on cell proliferation, cell cycle, and glycolysis were studied in vitro using a GEM-resistant (GEM-R) TNBC cell model. We enriched key pathways affected by GAD using proteomics techniques. Western blotting and qPCR were used to detect the expression of glycolysis-related genes after GAD treatment. A mouse resistance model was established using GEM-R TNBC cells, and hematoxylin-eosin staining and immunohistochemistry were used to assess the role of GAD in reversing resistance in vivo. RESULTS: Cellular functional assays showed that GAD significantly inhibited proliferation and glucose uptake in GEM-R TNBC cells. GAD reduces HIF-1α accumulation in TNBC cells under hypoxic conditions through the ubiquitinated protease degradation pathway. Mechanistically, GAD activates the p53/MDM2 pathway, promoting HIF-1α ubiquitination and proteasomal degradation and downregulating HIF-1α-dependent glycolysis genes like GLUT1, HK2, and PKM2. Notably, GAD combined with gemcitabine significantly reduced the growth of GEM-R TNBC cells in a subcutaneous tumor model. CONCLUSIONS: This study reveals a novel antitumor function of GAD, which inhibits glycolysis by promoting HIF-1α degradation in GEM-R TNBC cells, offering a promising therapeutic strategy for TNBC patients with GEM resistance.

Loss of polarity protein Par3 in the intestinal epithelium promotes colitis-associated colorectal cancer progression by damaging tight junction assembly.

Partitioning defective 3 (Par3) is a polarity protein critical in establishing epithelial cell polarity and tight junctions (TJs). Impaired intestinal epithelial barrier integrity is closely associated with colitis-associated colorectal cancer (CRC) progression. According to the GEO and TCGA database analyses, we first observed that the expression of Par3 was reduced in CRC patients. To understand how Par3 is related to CRC, we investigated the role of Par3 in the development of CRC using an in vivo genetic approach. Our results show that the intestinal epithelium-specific PAR3 deletion mice demonstrated a more severe CRC phenotype in the context of azoxymethane/dextran sodium sulfate (AOM/DSS) treatment, with a corresponding increase in tumor number and inflammatory cytokines profile. Mechanistically, loss of Par3 disrupts the TJs of the intestinal epithelium and increases mucosal barrier permeability. The interaction of Par3 with ZO-1 prevents intramolecular interactions within ZO-1 protein and facilitates the binding of occludin to ZO-1, hence preserving TJs integrity. Our results suggest that Par3 deficiency permits pathogenic bacteria and their endotoxins to penetrate the intestinal submucosa and activate TLR4/MyD88/NF-κB signaling, promoting inflammation-driven CRC development and that Par3 may be a novel potential molecular marker for the diagnosis of early-stage CRC.

Diagnosis and differential diagnosis of dermatofibrosarcoma protuberans: Utility of high-resolution dynamic contrast-enhanced (DCE) MRI.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a kind of low-grade malignant spindle cell neoplasm, the diagnosis, and treatment, which have markedly attracted clinicians' attention for its repeated recurrence. High-resolution magnetic resonance imaging (HR-MRI) has shown unique capabilities in diagnosis of various cutaneous tumors. MATERIALS AND METHODS: Data of 29 patients with clinically suspected DFSPs and undergoing dynamic contrast-enhanced (DCE) HR-MRI preoperatively were prospectively collected. The HR-MRI qualitative features were evaluated and compared. The DCE-associated quantitative parameters and the time-signal intensity curve (TIC) types were provided using DCE sequences. RESULTS: A total of 7 DFSPs, nine dermatofibromas (DF, including four cases of cellular variant [CDF]), 12 keloids, and one nodular fasciitis were enrolled. DFSP showed the largest major diameter and the deepest depth. Five DFSPs (71.4%) showed ill-defined margins as well as infiltration of peripheral adipose. All DFSPs showed irregular shape. Most DFSPs presented hyperintensity on T2 WI (71.4%) and iso-intensity on T1 WI (85.7%). Six cases (85.7%) had significant enhancement, and six cases (85.7%) had homogeneous enhancement. There were significant differences of Ktrans , Kep , Ve and iAUC values among DFSPs, DFs, and keloids, and DFSP had the highest values for these parameters. Six DFSPs (85.7%) and four CDFs (100%) showed type-III TICs, while the other lesions showed type-Ⅰor type-Ⅱ TICs. CONCLUSIONS: DCE-HR-MRI could show the growth characteristics of DFSPs, which was of great value for the diagnosis and differential diagnosis of DFSPs and was helpful for the determination of treatment options, thereby to improve the prognosis of patients.

Androgen Excess Induced Mitochondrial Abnormality in Ovarian Granulosa Cells in a Rat Model of Polycystic Ovary Syndrome.

Background: Androgen excess could profoundly lead to follicular dysplasia or atresia, and finally result in polycystic ovary syndrome (PCOS); however, the exact mechanism remains to be fully elucidated. Methods: PCOS model rats were induced by dehydroepiandrosterone, and their fertility was assessed. The ovarian granulosa cells (GCs) from matured follicles of PCOS model rats were collected and identified by immunofluorescence. The mitochondrial ultrastructure was observed by transmission electron microscope and the mitochondrial function was determined by detecting the adenosine triphosphate (ATP) content and mtDNA copy number. Besides, the expressions of respiratory chain complexes and ATP synthases in relation to mitochondrial function were analyzed. Results: The PCOS model rats were successfully induced, and their reproductive outcomes were obviously adverse. The GCs layer of the ovarian was apparently cut down and the mitochondrial ultrastructure of ovarian GCs was distinctly destroyed. The ATP content and mtDNA copy number of ovarian GCs in PCOS model rats were greatly reduced, and the expressions of NDUFB8 and ATP5j were significantly down-regulated without obvious deletion of mtDNA 4834-bp. Conclusions: Androgen excess could damage mitochondrial ultrastructure and function of GCs in rat ovary by down-regulating expression of NDUFB8 and ATP5j in PCOS.

A Rare Case of Cutaneous Intravascular NK/T-Cell Lymphoma.

BACKGROUND: Cutaneous intravascular NK/T cell lymphoma (CIVNKTC) is a rare form of extranodal non-Hodgkin's lymphoma with its unique histological and immunophenotypic characteristics. METHODS: We report a case presenting with an over 2-month history of nodules on the extremities and trunk with intermittent fever. Skin biopsy was taken from the patient and a histopathological examination was made from the material. RESULTS: The histopathological examination showed some expanding vessels filled with atypical lymphoid cells in the dermis and subcutaneous tissue. The tumor cells had large nuclei and one or two small nucleoli, with the expression of CD3, cytotoxic protein, and Epstein-Barr virus (EBV)-encoded messenger RNAs (EBER), and without the expression of tumor cytokeratin (CK), CD20, CD79A, CD4, and CD8. After being diagnosed as CIVNKTC and treated with a CHOP regimen 6 times, the patient died of this disease 1 year later. CONCLUSIONS: The clinical course is dangerous and the prognosis is extremely poor.

Baicalin inhibits recruitment of GATA1 to the HSD3B2 promoter and reverses hyperandrogenism of PCOS.

High androgen levels in patients suffering from polycystic ovary syndrome (PCOS) can be effectively reversed if the herb Scutellaria baicalensis is included in traditional Chinese medicine prescriptions. To characterize the effects of baicalin, extracted from S. baicalensis, on androgen biosynthesis in NCI-H295R cells and on hyperandrogenism in PCOS model rats and to elucidate the underlying mechanisms. The optimum concentration and intervention time for baicalin treatment of NCI-H295R cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and enzyme-linked immunosorbent assays. The functional genes affected by baicalin were studied by gene expression profiling (GEP), and the key genes were identified using a dual luciferase assay, RNA interference technique, and genetic mutations. Besides, hyperandrogenic PCOS model rats were induced and confirmed before and after baicalin intervention. As a result, Baicalin decreased the testosterone concentrations in a dose-and time-dependent manner in NCI-H295R cells. GEP revealed that 3ß-hydroxysteroid dehydrogenase type II (HSD3B2) was the key enzyme of androgen biosynthesis, and baicalin inhibited the expression of HSD3B2 by regulating the binding of transcription factor GATA-binding factor 1 (GATA1) to the HSD3B2 promoter. Hyperandrogenic PCOS model rats treated with baicalin significantly reversed the high androgen levels of serum and the abnormal ovarian status, restored the estrous cyclicity, and decreased the expression of HSD3B2 in ovarian. In summary , our data revealed that GATA1 is an important transcription factor activating the HSD3B2 promoter in steroidogenesis, and baicalin potentially be an effective therapeutic agent for hyperandrogenism in PCOS by inhibiting the recruitment of GATA1 to the HSD3B2 promoter in ovarian tissue.

An unusual case of folliculitis spinulosa decalvans.

We report the case of a 24-year-old man who presented with pustules, atrophic scars, and alopecia on the scalp, along with follicular keratotic papules on the cheeks, chest, abdomen, back, lateral upper arms, thighs, and axillae, of 6 years' duration. A diagnosis of folliculitis spinulosa decalvans (FSD) was made based on the clinical manifestation and histopathological findings. Dental examination also revealed dental anomalies and a fissured tongue, which are not known to be related to FSD. We provide an overview of the characteristic findings of FSD as well as a review of previously reported cases.

[Comprehensive traditional Chinese medicine intervention for perimenopausal syndrome in women: a community study].

BACKGROUND: As perimenopausal syndrome is a particularly disturbing condition to the patient, it is practical and necessary to establish a program of comprehensive traditional Chinese medicine therapy for women with perimenopausal syndrome. OBJECTIVE: To observe the therapeutic effects of a comprehensive traditional Chinese medicine therapy for women with perimenopausal syndrome in the community. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Women with perimenopausal syndrome who met the inclusion criteria in 3 communities of Shanghai were selected for this study. Comprehensive traditional Chinese medicine therapy, including administration of Chinese herbs, auricular point therapy, psychological counseling and the practice of Tai Chi, was applied for these women. MAIN OUTCOME MEASURES: The modified Kupperman index was measured once every 4 weeks for 12 weeks; the indexes of menopause-specific quality of life (MENQOL) questionnaire were measured before and after the treatment. RESULTS: There was no significant difference in 4 groups of negative conversion ratio of the modified Kupperman index at the 4th, 8th and 12th week, respectively. The indexes of the MENQOL questionnaire showed significant differences in 4 groups before and after the treatment. The overall efficacy rate of the comprehensive traditional Chinese medicine therapy in women with perimenopausal syndrome achieved 97.84% at the 8th and the 12th week. CONCLUSION: The comprehensive traditional Chinese medicine therapy can achieve significant improvements in women with perimenopausal syndrome who exhibit both physical and psychological symptoms. With such significant clinical effects, the comprehensive traditional Chinese medicine therapy should be promoted in the community.

Lactobacillus gasseri OLL2809 is effective especially on the menstrual pain and dysmenorrhea in endometriosis patients: randomized, double-blind, placebo-controlled study.

In this study, we evaluated the efficacy of Lactobacillus gasseri OLL2809 on endometriosis by the randomized, double-blind and placebo-controlled clinical study, especially against pain, which is one of the causative factors to decrease the quality of life. Sixty-six patients clinically diagnosed with endometriosis were enrolled in this study, 62 of which have successfully completed the trial. The tablets containing 100 mg of L. gasseri OLL2809 (active tablet, n = 29) or placebo tablets (n = 33) were ingested once a day for 12 weeks. Visual analog scale (VAS) of pain intensity at the menstrual period and verbal rating scale (VRS) of dysmenorrhea were significantly improved by the ingestion of the active tablets as compared with placebo tablets. There was no significant change of blood examination and biochemical examination of blood in the enrolled patients. Above results show that the tablet containing L. gasseri OLL2809 is effective on endometriosis, especially against menstrual pain and dysmenorrhea. Moreover, it was found that the tablet has no adverse effects. Therefore, it was suggested that the tablet containing L. gaserri OLL2809 contributes to improve the quality of life in the patients with endometriosis.