Heme catabolism and heme oxygenase-1-expressing myeloid cells in pathophysiology.

Although the pathological significance of myeloid cell heterogeneity is still poorly understood, new evidence indicates that distinct macrophage subsets are characterized by specific metabolic programs that influence disease onset and progression. Within this scenario, distinct subsets of macrophages, endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), play critical roles in physiologic and pathological conditions. Of relevance, the substrates of HO-1 activity are the heme groups that derive from cellular catabolism and are converted into carbon monoxide (CO), biliverdin and Fe2+, which together elicit anti-apoptotic, anti-inflammatory activities and control oxidative damage.

Debondable Epoxy-Acrylate Adhesives using β-Amino Ester Chemistry.

The reuse of multilayered materials, which are held together by structural epoxy adhesives, is a major challenge since the bonded substrates cannot be easily separated for recycling. In this research, we explore a one-pot strategy based on β-amino ester chemistry for the development of modified epoxy adhesives with on-demand debonding potential. For this, a formulation of commercially available acrylate, epoxy and amine compounds is used.

NKX3-2 Induces Ovarian Cancer Cell Migration by HDAC6-Mediated Repositioning of Lysosomes and Inhibition of Autophagy.

Several soluble factors secreted by the stromal cells and cancer cells within the tumor microenvironment facilitate the progression and invasiveness of ovarian cancer. In ovarian cancer cells, lysophosphatidic acid (LPA) modulates the transcriptome profile and promotes cell invasiveness by the downregulation of autophagy. Here, we further elucidate this mechanism by focusing on the molecular and cellular events regulating autophagy.

Symmetrical 2,7-disubstituted 9H-fluoren-9-one as a novel and promising scaffold for selective targeting of SIRT2.

Sirtuin 2 (SIRT2) belongs to the family of silent information regulators (sirtuins), which comprises nicotinamide adenine dinucleotide (NAD)-dependent protein lysine deacetylases. With a distribution across numerous tissues and organs of the human body, SIRT2 is involved in a wide range of physiological and pathological processes, such as regulating the cell cycle, energy metabolism, DNA repair, and tumorigenesis. Aberrant expression of SIRT2 has been closely associated with particular etiologies of human diseases, positioning SIRT2 as a promising therapeutic target.

Low ozone concentrations do not exert cytoprotective effects on tamoxifen-treated breast cancer cells .

Medical treatment with low ozone concentrations proved to exert therapeutic effects in various diseases by inducing a cytoprotective antioxidant response through the nuclear factor erythroid derived-like 2 (Nrf2) transcription factor pathway. Low ozone doses are increasingly administered to oncological patients as a complementary treatment to mitigate some adverse side-effects of antitumor treatments. However, a widespread concern exists about the possibility that the cytoprotective effect of Nrf2 activation may confer drug resistance to cancer cells or at least reduce the efficacy of antitumor agents.

Characterization of a decellularized pericardium extracellular matrix hydrogel for regenerative medicine: insights on animal-to-animal variability.

In the past years, the use of hydrogels derived from decellularized extracellular matrix (dECM) for regenerative medicine purposes has significantly increased. The intrinsic bioactive and immunomodulatory properties indicate these materials as promising candidates for therapeutical applications. However, to date, limitations such as animal-to-animal variability still hinder the clinical translation.

Unraveling Novel Strategies in Mesothelioma Treatments Using a Newly Synthetized Platinum(IV) Compound.

Malignant mesothelioma is a rare tumor associated with asbestos exposure. Mesothelioma carcinogenesis is related to enhanced reactive oxygen species (ROS) production and iron overload. Despite the recent advances in biomedical sciences, to date the only available treatments include surgery in a small fraction of patients and platinum-based chemotherapy in combination with pemetrexed.

Lack of association between TRPV1 gene polymorphisms and risk of migraine chronification: a case-control study and meta-analysis.

Objective: To confirm a previously reported association of TRPV1 rs8065080 with the risk of transformation from episodic (EM) to chronic migraine (CM) and to extend knowledge about the role of other TRPV1 single nucleotide polymorphisms (SNPs), we first investigated the impact of three TRPV1 SNPs (rs8065080, rs222747 and rs222749) on the risk of migraine chronification in a case-control study. A systematic review and meta-analysis were then conducted to summarize the accumulated findings.

Methods: Genotyping of the selected TRPV1 SNPs was performed using TaqMan real-time PCR in 167 EM and 182 CM participants.

Double-crosslinkable poly(urethane)-based hydrogels relying on supramolecular interactions and light-initiated polymerization: promising tools for advanced applications in drug delivery.

Physical and chemical hydrogels are promising platforms for tissue engineering/regenerative medicine (TERM). In particular, physical hydrogels are suitable for use in the design of drug delivery systems owing to their reversibility and responsiveness to applied stimuli and external environment. Alternatively, the use of chemical hydrogels represents a better strategy to produce stable 3D constructs in the TERM field.

A Phyto-mycotherapeutic Supplement, Namely , as Effective Adjuvant in Brain Cancer Management: An In Vitro Study Using U251 Human Glioblastoma Cell Line.

The current standard oncotherapy for glioblastoma is limited by several adverse side effects, leading to a short-term patient survival rate paralleled by a worsening quality of life (QoL). Recently, Complementary and Integrative Medicine's (CIM) innovative approaches have shown positive impacts in terms of better response to treatment, side effect reduction, and QoL improvement. In particular, promising potential in cancer therapy has been found in compounds coming from phyto- and mycotherapy.

2-(Methyl(phenyl)amino)-N-(phenyloxyphenyl)acetamide structural motif representing a framework for selective SIRT2 inhibition.

The mammalian cytoplasmic protein SIRT2, a class III histone deacetylase family member, possesses NAD-dependent lysine deacetylase/deacylase activity. Dysregulation of SIRT2 has been implicated in the pathogenesis of several diseases, including neurological and metabolic disorders and cancer; thus, SIRT2 emerges as a potential therapeutic target. Herein, we identified a series of diaryl acetamides (ST61-ST90) by the structural optimization of our hit STH2, followed by enhanced SIRT2 inhibitory potency and selectivity.

Safety and efficacy outcomes of early cessation of anti-PD1 therapy in patients 80 years or older: A retrospective cohort study.

Older patients have similar immune checkpoint inhibitor efficacy and rates of adverse events as younger patients, but appear to have decreased tolerability, particularly in the oldest patient cohort (>80 years), often leading to early cessation of therapy. We aimed to determine whether early discontinuation impacts efficacy of anti-PD-1 therapy in patients ≥80 years old. In this retrospective, multicenter, international cohort study, we examined 773 patients with 4 tumor types who were at least 80 years old and treated with anti-PD-1 therapy.

Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer.

Unlabelled: Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation of metabolites that reprogram the tumor microenvironment (TME) and drive cancer could facilitate development of precision nutrition approaches. Using the Hi-MYC prostate cancer mouse model, we demonstrated that an obesogenic high-fat diet (HFD) rich in saturated fats accelerates the development of c-MYC-driven invasive prostate cancer through metabolic rewiring.

Early Stage In Vitro Bioprofiling of Potential Low-Molecular-Weight Organoboron Compounds for Boron Neutron Capture Therapy (BNCT)-Proposal for a Guide.

Given the renewed interest in boron neutron capture therapy (BNCT) and the intensified search for improved boron carriers, as well as the difficulties of coherently comparing the carriers described so far, it seems necessary to define a basic set of assays and standardized methods to be used in the early stages of boron carrier development in vitro. The selection of assays and corresponding methods is based on the practical experience of the authors and is certainly not exhaustive, but open to discussion. The proposed tests/characteristics: Solubility, lipophilicity, stability, cytotoxicity, and cellular uptake apply to both low molecular weight (up to 500 Da) and high molecular weight (5000 Da and more) boron carriers.

An In Vitro Study on the Application of Silver-Doped Platelet-Rich Plasma in the Prevention of Post-Implant-Associated Infections.

Implant therapy is a common treatment option in dentistry and orthopedics, but its application is often associated with an increased risk of microbial contamination of the implant surfaces that cause bone tissue impairment. This study aims to develop two silver-enriched platelet-rich plasma (PRP) multifunctional scaffolds active at the same time in preventing implant-associated infections and stimulating bone regeneration. Commercial silver lactate (L) and newly synthesized silver deoxycholate:β-Cyclodextrin (B), were studied in vitro.

Impact of Tissue Damage and Hemodynamics on Restenosis Following Percutaneous Transluminal Angioplasty: A Patient-Specific Multiscale Model.

Multiscale agent-based modeling frameworks have recently emerged as promising mechanobiological models to capture the interplay between biomechanical forces, cellular behavior, and molecular pathways underlying restenosis following percutaneous transluminal angioplasty (PTA). However, their applications are mainly limited to idealized scenarios. Herein, a multiscale agent-based modeling framework for investigating restenosis following PTA in a patient-specific superficial femoral artery (SFA) is proposed.

Refining patient selection for next-generation immunotherapeutic early-phase clinical trials with a novel and externally validated prognostic nomogram.

Introduction: Identifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations.

Patients And Methods: We retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS).

Merits and boundaries of the BCLC staging and treatment algorithm: Learning from the past to improve the future with a novel proposal.

In this Expert Opinion, we thoroughly analyse the Barcelona Clinic Liver Cancer (BCLC) staging and treatment algorithm for hepatocellular carcinoma (HCC) that, since 1999, has standardised HCC management, offering a structured approach for the prognostic evaluation and treatment of patients with HCC. The first part of the article presents the strengths and evolutionary improvements of the BCLC staging system. Nevertheless, both patient characteristics and available treatments have changed in the last two decades, limiting the role of the BCLC criteria for treatment allocation in a growing number of patients.

Characterisation of Matrix-Bound Nanovesicles (MBVs) Isolated from Decellularised Bovine Pericardium: New Frontiers in Regenerative Medicine.

Matrix-bound nanovesicles (MBVs) are a recently discovered type of extracellular vesicles (EVs), and they are characterised by a strong adhesion to extracellular matrix structural proteins (ECM) and ECM-derived biomaterials. MBVs contain a highly bioactive and tissue-specific cargo that recapitulates the biological activity of the source ECM. The rich content of MBVs has shown to be capable of potent cell signalling and of modulating the immune system, thus the raising interest for their application in regenerative medicine.