Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer.

BACKGROUND: Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear. METHODS: The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo. RESULTS: Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells. CONCLUSIONS: Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer.

Spontaneous massive fetomaternal hemorrhage: two case reports and a literature review of placental pathology.

BACKGROUND: Massive fetomaternal hemorrhage (FMH) is a rare event during pregnancy that may cause severe fetal anemia or death. CASE PRESENTATION: This paper reports two cases of fetomaternal hemorrhage with unexplained reasons. Both cases required emergency caesarean sections for non-reassuring fetal status and were treated with neonatal blood transfusion. Fetomaternal hemorrhage was confirmed via maternal Kleihauer-Betke test. CONCLUSION: We found parenchymal pallor, increased nucleated red blood cells (nRBCs), and syncytial knots (SKs) in the placentas, which are compatible with fetal anemia. Immunohistochemical staining indicated VEGF, CD34, and CD31 expression in the endothelial cells of the capillaries, characteristic of massive FMH placenta. This article also reviews the particular histopathological changes in FHM placenta according to the placental lesion classification system.

Radioactive versus normal stent insertion for malignant hilar obstruction: a meta-analysis.

PURPOSE: This meta-analysis was designed for examining the relative clinical safety and efficacy of normal stent (NS) and radioactive stent (RS) insertion in malignant hilar obstruction (MHO) patients. MATERIAL AND METHODS: Relevant studies published as of March 2022 were identified through searches of the Medline, Embase, Wanfang, and CNKI databases, and the pooled results of these studies were then analyzed. RESULTS: Eight studies including 258 and 247 patients that underwent NS and RS insertion, respectively, were incorporated into this meta-analysis. RS insertion was found to be associated with significant improvements in functional successful rate (p = 0.04), Δaspertate aminotransferase (AST, p = 0.0004), Δalanine aminotransferase (ALT, p = 0.002), stent patency (p < 0.00001), stent re-obstruction rate (p = 0.03), and OS (p < 0.00001) outcomes as compared to those associated with NS insertion. No differences in Δtotal bilirubin (TBIL, p = 0.38), cholangeitis rate (p = 0.45), cholecystitis rate (p = 0.84), or hemorrhage rate (p = 0.87) were observed when comparing patients that underwent RS and NS insertion. Substantial publication bias was observed for endpoints of cholecystitis and hemorrhage. CONCLUSIONS: These results suggest that relative to NS insertion, RS insertion can effectively prolong stent patency and OS in MHO cases.

[Study on TYR gene variant from a pedigree with oculocutaneous albinism].

OBJECTIVE: To analyze gene variants in a Chinese pedigree with oculocutaneous albinism (OCA). METHODS: Gene sequencing of the proband and his parents was performed using chip capture high-throughput sequencing and Sanger sequencing techniques, and PolyPhen-2, SIFT, MutationTaster, and FATHMM software were used to predict the function of new variants. At the same time,the pedigree and variant genes of 4 albinism patients from this pedigree were analyzed. RESULTS: Sequencing results showed that the proband's TYR gene (NM_000372) has c.230G>A (p.Arg77Gln) and c.120_121insG (p.Asp42GlyfsTer35) compound heterozygous variants. The proband's father carries c.230G>A heterozygous variant, and the mother carries c.120_121insG heterozygous variant, indicating that the proband's two variants are from his father and mother. The former is a known missense variant, which can cause abnormal or loss of the original function of the protein polypeptide chain. The latter c.120_121insG(p.Asp42GlyfsTer35) is an unreported frameshift variant of the TYR gene subregion (EX1; CDS1). PolyPhen-2, SIFT, MutationTaster and FATHMM predictions are all prompted as "harmful variants". This variant caused the amino acid encoded protein to terminate prematurely, producing a truncated protein, which eventually formed a 76-amino acid short-type TYR protein instead of the 529-amino acid wild-type TYR protein. Through the pedigree analysis, the four patients in the pedigree are all of the same type of compound heterozygous variants, and the disease-causing genes are all from the patient's parents. They belong to a special form of consanguineous marriage within 5 generations. CONCLUSION: The compound heterozygous variants of c.230G>A (p.Arg77Gln) and c.120_121insG (p.Asp42GlyfsTer35) of the TYR gene may underlie the disease in this pedigree. The gene sequencing results enrich the variant spectrum of the TYR gene, and has facilitated molecular diagnosis for the patient.

Polysaccharide from Ziyang Selenium-Enriched Green Tea Prevents Obesity and Promotes Adipose Thermogenesis via Modulating the Gut Microbiota.

The objective of the current study was to explore the potential mechanism of Ziyang selenium-enriched green tea polysaccharide (Se-GTP) against obesity. The results showed that Se-GTP significantly alleviated obesity and related metabolic disorders caused by high-fat diet (HFD) in mice. 16S rRNA gene sequencing results revealed that Se-GTP improved gut microbiota disturbance of obese mice and facilitated proliferation of probiotics such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia. In addition, the colonic content of succinate, a product of microbial metabolite in connection with adipocyte thermogenesis, was significantly enhanced by Se-GTP treatment. Therefore, Se-GTP facilitated brown adipose tissue (BAT) thermogenesis and inguinal white adipose tissue (iWAT) browning in obese mice, which could be revealed by increased expressions of thermogenic marker proteins UCP1, PGC-1α, and CIDEA in BAT and iWAT. Interestingly, Se-GTP intervention also observably increased the content of M2-like macrophages in iWAT of obese mice. To summarize, the results of this study are the first to show that Se-GTP can stimulate the browning of iWAT and BAT thermogenesis to counteract obesity, which may be pertinent with the alteration of gut microbiota in obese mice.

Side-by-side versus stent-in-stent bilateral stenting for malignant hilar biliary obstruction: a meta-analysis.

Introduction: Both side-by-side (SBS) and stent-in-stent (SIS) bilateral stenting have been used for patients with malignant hilar biliary obstruction (MHBO). However, it is unclear which technique is better. Aim: This meta-analysis is conducted to investigate the clinical efficacy and safety of SBS and SIS bilateral stenting for patients with MHBO. Material and methods: Relevant studies were searched in PubMed, Embase, Cochrane Library, Wanfang, VIP, and CINK databases. The timeline for the searches was from the establishment of the database to September 2021. The relative outcomes are pooled. Results: A total of 7 studies fulfilled the inclusion criteria and entered into this meta-analysis. The pooled technical success rate was significant higher in the SIS group than that in the SBS group (p = 0.04). The pooled early complication rate was significantly lower in the SIS group than in the SBS group (p = 0.04). The pooled stent re-obstruction rate was significantly lower in the SBS group than in the SIS group (p = 0.04). The pooled stent patency duration was significantly longer in the SBS group than in the SIS group (p = 0.01). The pooled functional success rates (p = 0.79), total complication rates (p = 0.34), and overall survival duration (p = 0.27) were comparable between 2 groups. Egger test did not show any publication bias. Conclusions: When comparing the SBS and SIS bilateral stenting for patients with MHBO, although SIS technique may have the superiorities of technical success and early complication rates, the longer stent patency was achieved by the SBS technique.

Artemisia sphaerocephala Krasch polysaccharide promotes adipose thermogenesis and decreases obesity by shaping the gut microbiota.

This study was designed to investigate the underlying mechanism of Artemisia sphaerocephala Krasch polysaccharide (ASKP) against obesity. Here, our results showed that ASKP considerably reduced body weight gain and metabolic disorders in high fat diet (HFD)-fed mice. 16S rRNA gene sequencing revealed that ASKP relieved the gut microbiota disorder caused by HFD and promoted the proliferation of probiotics such as Lactobacillus, Bifidobacterium and Blautia. Interestingly, the fecal levels of succinate, a microbial metabolite associated with adipose thermogenesis, were dramatically elevated by ASKP treatment in obese mice. Accordingly, ASKP promoted thermogenesis of brown adipose tissue (BAT) and browning of inguinal white adipose tissue (iWAT) of mice fed with a HFD, as revealed by the elevated expression of thermogenic marker genes (UCP1, CIDEA and PGC1α) in BAT and iWAT. Importantly, antibiotic treatment significantly decreased the ASKP-elevated fecal levels of succinate and further abolished the adipose thermogenesis effects of ASKP. Taken together, our results show that ASKP prevents obesity through iWAT browning and BAT activation, a mechanism that is dependent on the gut microbiota metabolism.