Prevalence and spectrum of germline BRCA1 and BRCA2 in a cohort of ovarian cancer patients from the Salento peninsula (Southern Italy): a matter of preventive health.

OBJECTIVES: The aim of this exploratory, descriptive study was to characterize the deleterious BRCA1 and BRCA2 variants evaluated by genetic testing in a group of Ovarian cancer patients living in the Salento peninsula (Southern Italy). METHODS: From June 2014 to July 2023, patients with histologically confirmed high-grade serous carcinoma, fallopian tube, or primary peritoneal cancer who were referred to Lecce Familial Cancer Clinic were considered. BRCA-mutation genetic testing was performed on these patients. Socio-demographic data and cancer epidemiology were assessed, and Next Generation Sequencing and Sanger DNA sequencing were performed. RESULTS: The median age at the diagnosis of 332 ovarian cancer patients collected was 57 years. The pedigree analyses showed that 28.6% had familial cases and 39.7% had sporadic cases. Of the 319 patients submitted to genetic testing, 29.8% were carriers of BRCA1/2 mutation, 75.8% at BRCA1 and 24.2% at BRCA2 gene. Of the 21 BRCA1 mutations, the variant c.5266dupC was the most frequent alteration (28.4%). With respect to BRCA2, 13 mutations were found and the variant c.9676delT was the most frequently recorded (6.3%). CONCLUSIONS: This study reveals that the prevalence of germline mutations in the BRCA1 and BRCA2 genes was higher than reported by other studies. A broader understanding of the prevalence and role of BRCA mutations in development, response to treatment, and prognosis represents an exciting and developing area of ovarian cancer treatment and prevention.

The impact of SARS-CoV-2 on skeletal muscles.

In 2019-2020, the SARS-CoV-2 pandemic has shocked the world and most health care systems, and a "second wave" of the viral spread is ongoing in Europe and in Italy too. While, at the initial outbreak, the treatment of patients had focused on the respiratory symptoms, many diverse clinical manifestations of the disease have to date been reported. However, the complete course of the disease has not yet been fully clarified. In particular, several reports from the real-world clinical practice have highlighted the noxious effects of SARS-CoV-2 on skeletal muscles. In this brief review, we summarized the main current findings about muscular and neuromuscular damages that may be triggered by the virus or by the drugs used to treat COVID-19. Moreover, we underlined the need of attentive care and vigilance for patients with neuro-muscular disorders, who may be particularly susceptible to infection and at increased risk for severe COVID-19.

Trefoil factor family member 2 (Tff2) KO mice are protected from high-fat diet-induced obesity.

INTRODUCTION: Trefoil factor family member 2 (Tff2) is a small gut peptide, mainly known for its protective and healing functions. As previously demonstrated, high-fat (HF) feeding can rapidly and specifically modulate Tff2 transcription in key tissues of mice, including the duodenum and mesenteric adipose tissue, therefore suggesting a novel role for this gene in energy balance. DESIGN AND METHODS: To explore whether and how Tff2 can influence feeding behavior and energy metabolism, Tff2 knock-out (KO) mice were challenged with HF diet for 12 weeks, hence food and energy intakes, body composition, as well as energy excretion and serum lipid and hormonal levels were analyzed. Finally, energy efficiency was estimated. RESULTS: Tff2 KO mice showed a greater appetite and higher energy intake compared to wild-type (WT). Consistently, they presented lower levels of serum leptin, and increased transcription of agouti-related protein (Agrp) in the hypothalamus. Though energy and triglyceride fecal excretion were augmented in Tff2 KO mice, digestible energy intake was superior. However, KO mice were finally protected from HF diet-induced obesity, and accumulated less weight and fat depots than WT animals, while keeping a normal lean mass. Energy efficiency was lower in HF-KO mice, while energy expenditure and locomotor activity were globally increased. CONCLUSIONS: The present work demonstrates previously unsuspected roles for Tff2 and suggests it to be a mastermind in the control of energy balance and a promising therapeutic target for obesity.

A single dose of dihydrotestosterone induced a myogenic transcriptional program in female intra-abdominal adipose tissue.

Sex steroids are key regulators of adipose tissue (AT) mass, determining gender-specific differences in fat distribution and accumulation. With the aim of exploring the relevance and peculiarities of androgen action in female intra-abdominal AT, we used the serial analysis of gene expression (SAGE) method to analyze the AT transcriptome in four groups of female mice: intact, ovariectomized (OVX), OVX plus dihydrotestosterone (DHT) injection at 3h or 24h before sacrifice (DHT3h, DHT24h). An average of 19555 transcript species was examined in retroperitoneal fat. We found a total of 321 transcripts differentially modulated by DHT and OVX, including 125 novel genes. Several genes involved in energy metabolism/ATP production were up-regulated by DHT, whereas important regulators of lipid metabolism were reduced. Transcripts involved in Ca(2+) uptake/release, cell signalling, cell defence and protein expression were differentially modulated by DHT. A surprising number of myogenic genes were up-regulated, including myosin light and heavy polypeptides, troponins, as well as several actin-binding proteins. These results suggest that DHT24h may have induced a myogenic-like transcriptional program in adipocytes. The present study sheds light on the distinctive female transcriptional pattern acutely induced by androgens in intra-abdominal fat, and may add new insights into the global understanding of menopausal endocrinology and its association to intra-abdominal obesity.

Feeding regulates the expression of pancreatic genes in gastric mucosa.

The ineffective short-term control of feeding behavior compromises energy homeostasis and can lead to obesity. The gastrointestinal tract secretes several regulatory peptides. However, little is known about the stomach peptide contribution to the acute regulation of intake. In an attempt to identify new gastric signals, the serial analysis of gene expression (SAGE) method was used for the transcription profiling of stomach mucosa in 7 groups of mice: fasting and sacrificed 30 minutes, 1 hour, 3 hours after a low-fat (LF) or high-fat (HF) ad libitum meal. In total, 35 genes were differentially modulated by LF and HF meals compared to fasting, including 15 mRNAs coding for digestive enzymes/secretory proteins, and 10 novel transcripts. Although the basic expression profile did not undergo substantial variations, both LF and HF meals influenced the transcription. This study represents the first global analysis of stomach transcriptome as induced by different nutritional stimuli. Further studies including the characterization of novel genes may help to identify new targets for the therapy and prevention of obesity.

Feeding induced changes in the hypothalamic transcriptome.

BACKGROUND: Obesity is a complex multifactorial disorder which needs a comprehensive approach for prevention and treatment. We investigated the modifications in the hypothalamic gene expression induced by high-fat (HF) and low-fat (LF) meal ingestion in mice, in order to identify the signals rapidly mediating the hypothalamic control on energy intake. METHODS: After fasting, 1 group of mice was sacrificed and the others were fed ad libitum with HF or LF diet, and sacrificed 3 h after the beginning of the meal. The hypothalamus was sampled and the serial analysis of gene expression method was performed. RESULTS: Approximately 254,588 tags, which correspond to 65,548 tag species were isolated from the 3 groups. The data showed twelve transcripts regulated by food intake. Among these, 2 transcripts have mitochondrial functions (MtCo1, Ppid), 3 are involved in protein transport and regulation (Ube2q2, Mup1, Sec13), 1 in cellular pH control (Slc4a3) and another 1 has a role in the epigenetic control of gene expression (Setd3). In addition, 5 potentially novel transcripts were differentially modulated. CONCLUSION: We identified genes that may regulate hypothalamic circuits governing the early response to food intake. 3 genes were specifically modulated by high-fat intake.