Structuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery.

Lipid nanoparticles (LNPs) play a crucial role in addressing genetic disorders, and cancer, and combating pandemics such as COVID-19 and its variants. Yet, the ability of LNPs to effectively encapsulate large-size DNA molecules remains elusive. This is a significant limitation, as the successful delivery of large-size DNA holds immense potential for gene therapy.

Dilated cardiomyopathy due to a novel combination of TTN and BAG3 genetic variants: From acute heart failure to subclinical phenotypes.

Dilated cardiomyopathy (DCM) is defined as left ventricular enlargement accompanied by systolic dysfunction not explained by abnormal loading conditions or coronary heart disease. The DCM clinical spectrum is broad, ranging from subclinical to severe presentation with progression to end stage heart failure. To date, different genetic loci have been found to have moderate/definitive evidence for causality in DCM and pathogenic variants in the TTN gene represent the main genetic determinant.

pH-sensitive niosomes for ATRA delivery: A promising approach to inhibit Pin1 in high-grade serous ovarian cancer.

The peptidyl-prolyl cis/trans isomerase Pin1 positively regulates numerous cancer-driving pathways, and it is overexpressed in several malignancies, including high-grade serous ovarian cancer (HGSOC). The findings that all-trans retinoic acid (ATRA) induces Pin1 degradation strongly support that ATRA treatment might be a promising approach for HGSOC targeted therapy. Nevertheless, repurposing ATRA into the clinics for the treatment of solid tumors remains an unmet need mainly due to the insurgence of resistance and its ineffective delivery.

Wasserstein barycenter regression for estimating the joint dynamics of renewable and fossil fuel energy indices.

In order to characterize non-linear system dynamics and to generate term structures of joint distributions, we propose a flexible and multidimensional approach, which exploits Wasserstein barycentric coordinates for histograms. We apply this methodology to study the relationships between the performance in the European market of the renewable energy sector and that of the fossil fuel energy one. Our methodology allows us to estimate the term structure of conditional joint distributions.

The (IOSPS-HW): Development and Psychometric Properties of a New Instrument to Assess Individual and Organizational Stress Factors in Periods of Pandemics.

The validation and psychometric properties of the (IOSPS-HW) were presented. This is a new measure to assess individual factors related to the health and well-being of individuals, such as family and personal relationships, as well as organizational factors related to the management of the pandemic, including workplace relationships, job management and communication. Across two studies conducted at different time points of the pandemic, psychometric evidence of the IOSPS-HW is presented.

Impact of Covid-19 pandemic on children with special needs requiring general anaesthesia for the treatment of dental disease: the experience of the Brescia Children's Hospital, Lombardy, Italy.

Purpose: Special needs children presenting with dental problems were penalised during the Covid-19 pandemic due to the reduction of clinical activity and the risks of nosocomial infection. The aim of this study is to evaluate the impact of the pandemic on oral healthcare in paediatric special needs patients.

Methods: We retrospectively assessed and compared the outpatient clinic activity and dental procedures performed under general anaesthesia in children with special needs at Brescia Children's Hospital (Italy) in 2019, 2020, and 2021.

5FU/Oxaliplatin-Induced Jagged1 Cleavage Counteracts Apoptosis Induction in Colorectal Cancer: A Novel Mechanism of Intrinsic Drug Resistance.

Colorectal cancer (CRC) is characterized by early metastasis, resistance to anti-cancer therapy, and high mortality rate. Despite considerable progress in the development of new treatment options that improved survival benefits in patients with early-stage or advanced CRC, many patients relapse due to the activation of intrinsic or acquired chemoresistance mechanisms. Recently, we reported novel findings about the role of Jagged1 in CRC tumors with Kras signatures.

Notch signaling in female cancers: a multifaceted node to overcome drug resistance.

Drug resistance is one of the main challenges in cancer therapy, including in the treatment of female-specific malignancies, which account for more than 60% of cancer cases among women. Therefore, elucidating the underlying molecular mechanisms is an urgent need in gynecological cancers to foster novel therapeutic approaches. Notably, Notch signaling, including either receptors or ligands, has emerged as a promising candidate given its multifaceted role in almost all of the hallmarks of cancer.

Opsonin-Deficient Nucleoproteic Corona Endows UnPEGylated Liposomes with Stealth Properties .

For several decades, surface grafted polyethylene glycol (PEG) has been a go-to strategy for preserving the synthetic identity of liposomes in physiological milieu and preventing clearance by immune cells. However, the limited clinical translation of PEGylated liposomes is mainly due to the protein corona formation and the subsequent modification of liposomes' synthetic identity, which affects their interactions with immune cells and blood residency. Here we exploit the electric charge of DNA to generate unPEGylated liposome/DNA complexes that, upon exposure to human plasma, gets covered with an opsonin-deficient protein corona.

Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response.

Unfolded protein response (UPR) is a conserved adaptive response that tries to restore protein homeostasis after endoplasmic reticulum (ER) stress. Recent studies highlighted the role of UPR in acute leukemias and UPR targeting has been suggested as a therapeutic approach. Aberrant Notch signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL), as downregulation of Notch activity negatively affects T-ALL cell survival, leading to the employment of Notch inhibitors in T-ALL therapy.

ProAlanase is an Effective Alternative to Trypsin for Proteomics Applications and Disulfide Bond Mapping.

Trypsin is the protease of choice in bottom-up proteomics. However, its application can be limited by the amino acid composition of target proteins and the pH of the digestion solution. In this study we characterize ProAlanase, a protease from the fungus that cleaves primarily on the C-terminal side of proline and alanine residues.

Current Trends in ATRA Delivery for Cancer Therapy.

All-Trans Retinoic Acid (ATRA) is the most active metabolite of vitamin A. It is critically involved in the regulation of multiple processes, such as cell differentiation and apoptosis, by activating specific genomic pathways or by influencing key signaling proteins. Furthermore, mounting evidence highlights the anti-tumor activity of this compound.

Italian multi-society modified Delphi consensus on the definition and management of anastomotic leakage in colorectal surgery.

Introduction: The incidence of anastomotic leak (AL) has not decreased over the past decades and some important grey areas remain in its definition, prevention, and management. The aim of this study was to reach a national consensus on the definition of AL and to identify key points to be applied in clinical practice.

Methods: A 3-step modified Delphi method was used to establish consensus.

Notch Signaling Activation as a Hallmark for Triple-Negative Breast Cancer Subtype.

Triple-negative breast cancer (TNBC) is a subgroup of 15%-20% of diagnosed breast cancer patients. It is generally considered to be the most difficult breast cancer subtype to deal with, due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), which usually direct targeted therapies. In this scenario, the current treatments of TNBC-affected patients rely on tumor excision and conventional chemotherapy.

Prolyl-isomerase Pin1 controls Notch3 protein expression and regulates T-ALL progression.

Deregulated Notch signaling is associated with T-cell Acute Lymphoblastic Leukemia (T-ALL) development and progression. Increasing evidence reveals that Notch pathway has an important role in the invasion ability of tumor cells, including leukemia, although the underlying molecular mechanisms remain mostly unclear. Here, we show that Notch3 is a novel target protein of the prolyl-isomerase Pin1, which is able to regulate Notch3 protein processing and to stabilize the cleaved product, leading to the increased expression of the intracellular domain (N3IC), finally enhancing Notch3-dependent invasiveness properties.

The SIC-GIRCG 2013 Consensus Conference on Gastric Cancer.

The topic chosen by the Board of the Italian Society of Surgery for the 2013 annual Consensus Conference was gastric cancer. With this purpose, under the direction of 2 chairmen, 36 experts nominated by the Regional Societies of Surgery and by the Italian Research Group for Gastric Cancer (GIRCG) participated in an experts consensus exercise, preceded by a questionnaire and mainly held by telematic vote, in accordance with the rules of the Delphi method. The results of this Consensus Conference, presented to the 115th National Congress of the Italian Society of Surgery, and approved in plenary session, are reported in the present paper.

Bone metastases in gastric cancer follow a RANKL-independent mechanism.

Gastric cancer is one of the most common and lethal malignancies worldwide. Bone metastases in gastric cancer are less common than in other solid tumors, but when they occur the prognosis is generally poor. Increased osteoclastogenesis and osteoclast activity are common features in bone metastases caused by different osteotropic cancer.

Prevalence of Helicobacter pylori infection and intestinal metaplasia in subjects who had undergone surgery for gastric adenocarcinoma in Northwest Italy.

Aim: To investigate the seroprevalence of Helicobacter pylori (H pylori) infection and its more virulent strains as well as the correlation with the histologic features among patients who had undergone surgery for gastric cancer (GC).

Methods: Samples from 317 (184 males, 133 females, mean age 69+/-3.4 years) consecutive patients who had undergone surgery for gastric non-cardia adenocarcinoma were included in the study.

ERCP and acute pancreatitis.

Acute biliary pancreatitis (ABP) is a serious complication of biliary stones disease and is associated with significant morbidity and mortality. The role of ERCP in the management of ABP has been the focus of discussion in recent years. In this report, we evaluated a protocol of emergency Endoscopic retrograde Cholangiopancreatography (ERCP) (within 24 hours) and early ERCP (within 72 hours).

Large postoperative umbilical hernia following laparoscopic cholecystectomy. A case report.

The authors report a case of large postoperative umbilical hernia following laparoscopic cholecystectomy, which occurred in the early postoperative period despite primary suture of the trocar insertion site. Forced dilation of the fascial layer is proposed as the etiological mechanism. This procedure should be avoided and an accurate and aseptic removal of the gallbladder should be performed in order to prevent risk of abdominal wall weakness and visceral herniation.