HMGB1, an evolving pleiotropic protein critical for cellular and tissue homeostasis: Role in aging and age-related diseases.

Aging is a universal biological process characterized by a progressive, cumulative decline in homeostatic capabilities and physiological functions, which inevitably increases vulnerability to diseases. A number of molecular pathomechanisms and hallmarks of aging have been recognized, yet we miss a thorough understanding of their complex interconnectedness. This review explores the molecular and cellular mechanisms underlying human aging, with a focus on the multiple roles of high mobility group Box 1 protein (HMGB1), the archetypal damage-associated molecular pattern (DAMP) molecule.

Circulating extracellular vesicles are monitoring biomarkers of anti-PD1 response and enhancer of tumor progression and immunosuppression in metastatic melanoma.

Background: Clinical drawback in checkpoint inhibitors immunotherapy (ICI) of metastatic melanoma (MM) is monitoring clinical benefit. Soluble forms of PD1(sPD1) and PD-L1(sPD-L1) and extracellular vesicles (EVs) expressing PD1 and PD-L1 have recently emerged as predictive biomarkers of response. As factors released in the blood, EVs and soluble forms could be relevant in monitoring treatment efficacy and adaptive resistance to ICI.

Campylobacter and risk factors associated with dog ownership: a retrospective study in household and in shelter dogs.

Campylobacteriosis has been the most frequently reported zoonotic disease in humans in Europe. The scientific literature has reported that the role of dogs may be relevant. The objectives of this work are to improve the knowledge about Campylobacter spp.

Cancer cachexia as a multiorgan failure: Reconstruction of the crime scene.

Cachexia is a devastating syndrome associated with the end-stage of several diseases, including cancer, and characterized by body weight loss and severe muscle and adipose tissue wasting. Although different cancer types are affected to diverse extents by cachexia, about 80% of all cancer patients experience this comorbidity, which highly reduces quality of life and response to therapy, and worsens prognosis, accounting for more than 25% of all cancer deaths. Cachexia represents an urgent medical need because, despite several molecular mechanisms have been identified, no effective therapy is currently available for this devastating syndrome.

Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy.

Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices.

Remote mentoring in laparotomic and laparoscopic cancer surgery during Covid-19 pandemic: an experimental setup based on mixed reality.

In this paper, Mixed Reality (MR) has been exploited in the operating rooms to perform laparoscopic and open surgery with the aim of providing remote mentoring to the medical doctors under training during the Covid-19 pandemic. The employed architecture, which has put together MR smartglasses, a Digital Imaging Player, and a Mixed Reality Toolkit, has been used for cancer surgery at the IRCCS Hospital 'Giovanni Paolo II' in southern Italy. The feasibility of using the conceived platform for real-time remote mentoring has been assessed on the basis of surveys distributed to the trainees after each surgery.

Rebalancing expression of HMGB1 redox isoforms to counteract muscular dystrophy.

Muscular dystrophies (MDs) are a group of genetic diseases characterized by progressive muscle wasting associated to oxidative stress and persistent inflammation. It is essential to deepen our knowledge on the mechanism connecting these two processes because current treatments for MDs have limited efficacy and/or are associated with side effects. Here, we identified the alarmin high-mobility group box 1 (HMGB1) as a functional link between oxidative stress and inflammation in MDs.

Lights and Shade of Next-Generation Pi3k Inhibitors in Chronic Lymphocytic Leukemia.

The treatment (i.e. therapy and management) of chronic lymphocytic leukemia (i.

The Interaction of the Tumor Suppressor FAM46C with p62 and FNDC3 Proteins Integrates Protein and Secretory Homeostasis.

FAM46C is a non-canonical poly(A) polymerase uniquely mutated in up to 20% of multiple myeloma (MM) patients, implying a tissue-specific tumor suppressor function. Here, we report that FAM46C selectively stabilizes mRNAs encoding endoplasmic reticulum (ER)-targeted proteins, thereby concertedly enhancing the expression of proteins that control ER protein import, folding, N-glycosylation, and trafficking and boosting protein secretion. This role requires the interaction with the ER membrane resident proteins FNDC3A and FNDC3B.

Oxidation of HMGB1 Is a Dynamically Regulated Process in Physiological and Pathological Conditions.

Acute inflammation is a complex biological response of tissues to harmful stimuli, such as pathogens or cell damage, and is essential for immune defense and proper healing. However, unresolved inflammation can lead to chronic disorders, including cancer and fibrosis. The High Mobility Group Box 1 (HMGB1) protein is a Damage-Associated Molecular Pattern (DAMP) molecule that orchestrates key events in inflammation by switching among mutually exclusive redox states.

An Intrapancreatic accessory spleen presenting as a neuroendocrine tumor.

Although the second most common site of the accessory spleen is the tail of the pancreas, intrapancreatic accessory spleens (IPAS) are rarely recognized radiologically. When an accessory spleen is located in the pancreas, it may mimic a hypervascular pancreatic tumor. We report a case of intrapancreatic accessory spleen which radiologically (on TC) mimicked a neuroendocrine pancreatic tumor (PNET).

Immunohistochemical investigations on Brucella ceti-infected, neurobrucellosis-affected striped dolphins (Stenella coeruleoalba).

Bacteria of the genus Brucella cause brucellosis, an infectious disease common to humans as well as to terrestrial and aquatic mammals. Since 1994 several cases of Brucella spp. infection have been reported in marine mammals worldwide.

Synergism of Adipocytokine Profile and Polymorphisms in NAFLD-associated MetS Predict Colorectal Liver Metastases Outgrowth.

Background/aim: The aim of this study was to evaluate whether the altered profile of adipocytokine and genetic fingerprint in NAFLD-associated metabolic syndrome "cluster" represents synergistic risk factors predicting onset of liver colorectal cancer metastases.

Materials And Methods: A total of 165 colorectal cancer patients were enrolled, 56,3% were with metabolic syndrome/NAFLD. Serum samples were assayed for ADIPOQ, leptin and TNF-a levels by ELISA.

The Management of Oligoprogression in the Landscape of New Therapies for Metastatic Melanoma.

: A limited degree of progression after a response to treatment is labelled as oligoprogression and is a hot topic of metastatic melanoma (MM) management. Rogue progressive metastases could benefit from local treatment, which could allow the continuation of ongoing systemic therapy, also known as treatment beyond progression (TBP). : We retrospectively reviewed 214 selected MM patients who developed oligoprogression during treatment with v-Raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen-activated-extracellular signal-regulated kinase (MEK) or programmed cell death protein 1 (PD-1) inhibitors and received a local treatment continuing TBP.

Autophagy mediates epithelial cancer chemoresistance by reducing p62/SQSTM1 accumulation.

To cope with intrinsic and environmental stress, cancer cells rely on adaptive pathways more than non-transformed counterparts. Such non-oncogene addiction offers new therapeutic targets and strategies to overcome chemoresistance. In an attempt to study the role of adaptive pathways in acquired drug resistance in carcinoma cells, we devised a model of in vitro conditioning to three standard chemotherapeutic agents, cisplatin, 5-fluorouracil, and docetaxel, from the epithelial cancer cell line, HEp-2, and investigated the mechanisms underlying reduced drug sensitivity.

Bartonella infections in humans dogs and cats.

Bartonellae are emerging vector-borne pathogens distributed worldwide that can cause various clinical symptoms in humans and animals, ranging from a mild flu-like illness to more severe manifestations such as endocarditis, myocarditis, arthritis, hepatitis, and arthralgia. Numerous mammalian species, including domestic animals such as dogs, cats, as well as humans, serve as reservoir hosts for various Bartonella species. The vectors play a central role in the transmission of these bacteria and pets and their ectoparasites can pose a serious risk of zoonoses.

Preliminary validity of the modified Cigarette Evaluation Questionnaire in predicting the reinforcing effects of cigarettes that vary in nicotine content.

Validity studies evaluating self-report measures in relation to behavioral preference of cigarettes varying in nicotine content are needed. The current study examined the relationship between ratings on the modified Cigarette Evaluation Questionnaire (mCEQ) and the relative reinforcing effects of Spectrum research cigarettes (15.8, 5.

Campylobacter infections, a significant issue of veterinary urban hygiene: dog‑related risk factors.

Campylobacter spp. are ubiquitous bacteria and campylobacteriosis is the most frequently reported zoonotic disease in humans in Europe, since 2005. Handling or consuming contaminated/undercooked meat (especially poultry) are the most important sources of human campylobacteriosis.

Assessment of Nutritional and Inflammatory Status to Determine the Prevalence of Malnutrition in Patients Undergoing Surgery for Colorectal Carcinoma.

Background/aim: Colorectal Cancer is the fourth most frequent cause of cancer death worldwide and its incidence increases from 50 years of age. It is often associated with protein-caloric malnutrition and 20% of cancer deaths occur due to this event. The aim of this study was to assess the prevalence of malnutrition and inflammatory status in 78 patients undergoing surgery for colorectal carcinoma.

A 10-Year Review of Total Hospital-Onset ICU Bloodstream Infections at an Academic Medical Center.

Background: The rates of central line-associated bloodstream infections (CLABSIs) in U.S. ICUs have decreased significantly, and a parallel reduction in the rates of total hospital-onset bacteremias in these units should also be expected.

Lethal distemper in badgers (Meles meles) following epidemic in dogs and wolves.

Canine distemper virus (CDV) represents an important conservation threat to many wild carnivores. A large distemper epidemic sustained by an Arctic-lineage strain occurred in Italy in 2013, mainly in the Abruzzi region, causing overt disease in domestic and shepherd dogs, Apennine wolves (Canis lupus) and other wild carnivores. Two badgers were collected by the end of September 2015 in a rural area of the Abruzzi region and were demonstrated to be CDV-positive by real time RT-PCR and IHC in several tissues.

Microvascular density and endothelial area correlate with Ki-67 proliferative index in surgically-treated pancreatic ductal adenocarcinoma patients.

Previous experimental and clinical data have indicated that tumour cell proliferation is associated with angiogenesis; in addition, an increased microvascular density (MVD) of tumours has been associated with poor prognosis in solid and haematological malignancies. However, limited data exists regarding the association between tumour cell proliferation and angiogenesis in primary tumour tissue from pancreatic ductal adenocarcinoma (PDAC) patients; therefore, the present study aimed to investigate this association. A series of 31 PDAC patients with stage Tumour (T) Node (N) Metastasis (M) were recruited into the present study and subsequently underwent surgery.