Targeting Dectin-1 and or VISTA enhances anti-tumor immunity in melanoma but not colorectal cancer model.

Purpose: Acquired resistance to immune checkpoint blockers (ICBs) is a major barrier in cancer treatment, emphasizing the need for innovative strategies. Dectin-1 (gene Clec7a) is a C-type lectin receptor best known for its ability to recognize β-glucan-rich structures in fungal cell walls. While Dectin-1 is expressed in myeloid cells and tumor cells, its significance in cancer remains the subject of controversy.

Telerehabilitation with ARC Intellicare to Cope with Motor and Respiratory Disabilities: Results about the Process, Usability, and Clinical Effect of the "Ricominciare" Pilot Study.

Background: "Ricominciare" is a single-center, prospective, pre-/post-intervention pilot study aimed at verifying the feasibility and safety of the ARC Intellicare (ARC) system (an artificial intelligence-powered and inertial motion unit-based mobile platform) in the home rehabilitation of people with disabilities due to respiratory or neurological diseases.

Methods: People with Parkinson's disease (pwPD) or post-COVID-19 condition (COV19) and an indication for exercise or home rehabilitation to optimize motor and respiratory function were enrolled. They underwent training for ARC usage and received an ARC unit to be used independently at home for 4 weeks, for 45 min 5 days/week sessions of respiratory and motor patient-tailored rehabilitation.

CD71+VISTA+ erythroid cells promote the development and function of regulatory T cells through TGF-β.

Cell-surface transferrin receptor (CD71+) erythroid cells are abundant in newborns with immunomodulatory properties. Here, we show that neonatal CD71+ erythroid cells express significant levels of V-domain Immunoglobulin (Ig) Suppressor of T Cell Activation (VISTA) and, via constitutive production of transforming growth factor (TGF)- β, play a pivotal role in promotion of naïve CD4+ T cells into regulatory T cells (Tregs). Interestingly, we discovered that CD71+VISTA+ erythroid cells produce significantly higher levels of TGF-β compared to CD71+VISTA- erythroid cells and CD71+ erythroid cells from the VISTA knock-out (KO) mice.

VISTA deficiency attenuates antibody-induced arthritis and alters macrophage gene expression in response to simulated immune complexes.

Background: In addition to activated T cells, the immune checkpoint inhibitor "V domain-containing Ig suppressor of T-cell activation" (VISTA) is expressed by myeloid cell types, including macrophages and neutrophils. The importance of VISTA expression by myeloid cells to antibody-induced arthritis and its potential for relevance in human disease was evaluated.

Methods: VISTA was immunolocalized in normal and arthritic human synovial tissue sections and synovial tissue lysates were subjected to western blot analysis.

Magnetic fields exposure from high-voltage power lines and risk of amyotrophic lateral sclerosis in two Italian populations.

The aetiology of amyotrophic lateral sclerosis (ALS), a rare and extremely severe neurodegenerative disease, has been associated with magnetic fields exposure. However, evidence for such a relation in the general population is weak, although the previous null results might also be due to exposure misclassification, or a relationship might exist only for selected subgroups. To test such a hypothesis we carried out a population-based case-control study in two Northern and Southern Italy regions, including 703 ALS cases newly diagnosed from 1998 to 2011 and 2737 controls randomly selected from the residents in the study provinces.

Evaluation of early changes induced by diuron in the rat urinary bladder using different processing methods for scanning electron microscopy.

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substituted urea herbicide carcinogenic to the rat urinary bladder at high dietary levels. The suggested non-genotoxic mode of action (MOA) of diuron encompasses cytotoxicity and necrosis followed by regenerative hyperplasia. Prenecrotic swollen cells as observed under scanning electron microscopy (SEM) have been reported as early morphological alterations, putatively related to diuron cytotoxicity.

Can single use negative pressure wound therapy be an alternative method to manage keloid scarring? A preliminary report of a clinical and ultrasound/colour-power-doppler study.

Keloid scarring represents a pathological healing where primary healing phenomenon is deviated from normal. Pico is a single use negative pressure wound therapy system originally introduced to manage open or just closed wounds. Pico dressing is made of silicone, and distributes an 80 mmHg negative pressure across wound bed.

AUF1/hnRNP D represses expression of VEGF in macrophages.

Vascular endothelial growth factor (VEGF) is a regulator of vascularization in development and is a key growth factor in tissue repair. In disease, VEGF contributes to vascularization of solid tumors and arthritic joints. This study examines the role of the mRNA-binding protein AUF1/heterogeneous nuclear ribonucleoprotein D (AUF1) in VEGF gene expression.

Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjögren's syndrome.

Introduction: In Sjögren's syndrome, keratoconjunctivitis sicca (dry eye) is associated with infiltration of lacrimal glands by leukocytes and consequent losses of tear-fluid production and the integrity of the ocular surface. We investigated the effect of blockade of the lymphotoxin-beta receptor (LTBR) pathway on lacrimal-gland pathology in the NOD mouse model of Sjögren's syndrome.

Methods: Male NOD mice were treated for up to ten weeks with an antagonist, LTBR-Ig, or control mouse antibody MOPC-21.

VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses.

The immunoglobulin (Ig) superfamily consists of many critical immune regulators, including the B7 family ligands and receptors. In this study, we identify a novel and structurally distinct Ig superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1. This molecule is designated V-domain Ig suppressor of T cell activation (VISTA).

Inhibition of arterial lesion progression in CD16-deficient mice: evidence for altered immunity and the role of IL-10.

Aims: Given the importance of IgG Fc receptors in immune regulation, we hypothesized that Fcg receptor type III (FcgRIII, CD16) plays an important role in atherogenesis. We therefore analysed the formation of arterial lesions in LDL receptor-deficient (LDLR(-/-)) and FcgRIII(-/-)xLDLR(-/-) double knockout mice at three different points up to 24 weeks of exposure to a high-fat diet.

Methods And Results: Analysis of Oil Red-O-stained sections revealed no difference in lesion formation between strains after 6 weeks of a high-fat diet, and a modest decrease after 14 weeks in double knockouts relative to LDLR(-/-) controls.

Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjögren's syndrome in salivary glands of non-obese diabetic mice.

Introduction: The lymphotoxin-beta receptor (LTbetaR) pathway is important in the development and maintenance of lymphoid structures. Blocking this pathway has proven beneficial in murine models of autoimmune diseases such as diabetes and rheumatoid arthritis. The aim of this study was to determine the effects of LTbetaR pathway blockade on Sjögren syndrome (SS)-like salivary gland disease in non-obese diabetic (NOD) mice.

Speech perception ability in individuals with Friedreich ataxia.

The aim of this study was to investigate auditory pathway function and speech perception ability in individuals with Friedreich ataxia (FRDA). Ten subjects confirmed by genetic testing as being homozygous for a GAA expansion in intron 1 of the FXN gene were included. While each of the subjects demonstrated normal, or near normal sound detection, 3 of the 10 showed electrophysiological evidence of auditory pathway disorder [presenting with the auditory neuropathy/dyssynchrony (AN/AD) result pattern], and 9 of the 10 showed abnormal speech understanding when tested with levels of background noise typical of everyday listening conditions.

Distally based fasciocutaneous sural flap for foot reconstruction: a retrospective review of 10 years experience.

Background: The treatment of soft tissue defects of the foot is a problem mainly connected to the thickness of the coverage tissues, to the poor circulation, and to the frequent involvement of muscle, tendon, and bone. The authors present their experience with the sural flap, also in some particular cases.

Materials And Methods: The authors treated 33 patients for small- and medium-size defects of the foot, caused by work, home, and road accidents, and by venous or diabetic ulcers.

A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling.

Stat5 proteins are critical signaling molecules activated by many cytokines. Within the immune system, Stat5 plays important roles related to the development of thymocytes and proliferation of T cells. Stat5 has been implicated in malignant transformation, and moreover, the activated tyrosine phosphorylated form of Stat5 is frequently observed in human lymphomas.

The synthetic triterpenoid TP-222 inhibits RANKL stimulation of osteoclastogenesis and matrix metalloproteinase-9 expression.

Objective: Receptor activator of nuclear factor-kappaB ligand (RANKL) promotes osteoclast differentiation from monocyte precursors by inducing a cohort of genes, including tartrate-resistant acid phosphatase (TRAP) and matrix metalloproteinase-9 (MMP-9). A family of synthetic triterpenoids with antiinflammatory and pro-apoptotic properties was described to modulate differentiation in monocytic cell lineages. We therefore investigated the ability of the potent and bioavailable synthetic triterpenoid TP-222 to inhibit RANKL-induced osteoclast formation and MMP-9 expression from monocytic precursor cells.

Lymphotoxin-beta receptor signaling is required for the homeostatic control of HEV differentiation and function.

The lymphotoxin axis is important for the maintenance of several specialized lymphoid microenvironments in secondary lymphoid tissue. Lymphoid-tissue architecture is highly plastic and requires continual homeostatic signaling to maintain its basal functional state. The cellularity of lymph nodes in adult mice was reduced by systemic blockade of lymphotoxin-beta receptor (LTbeta R) signaling with a soluble decoy receptor both in resting and reactive settings.

Quantitative ultrasound measurements of the calcaneus in the prediction of lumbar spine degeneration.

A cross-sectional study was conducted to evaluate the possible use of a low-cost radiation-free technique in the prediction of degenerative changes in the lumbar spine. Although an inverse correlation between osteoporosis and degenerative changes in the lumbar spine has been reported, no previous studies have asked whether there is a correlation between calcaneal quantitative ultrasound results and degenerative findings in the lumbar spine. In 117 patients with low back pain or pain in the lower limb, ultrasonographic parameters (speed of sound, broadband ultrasound attenuation, stiffness) of the calcaneus were correlated with evidence of degenerative changes and stenosis on magnetic resonance scans of the lumbar spine.

A role for the lymphotoxin/LIGHT axis in the pathogenesis of murine collagen-induced arthritis.

A lymphotoxin-beta (LTbeta) receptor-Ig fusion protein (LTbetaR-Ig) was used to evaluate the importance of the lymphotoxin/LIGHT axis in the development and perpetuation of arthritis. Prophylactic treatment with the inhibitor protein LTbetaR-Ig blocked the induction of collagen-induced arthritis in mice and adjuvant arthritis in Lewis rats. Treatment of mice with established collagen-induced arthritis reduced the severity of arthritic symptoms and joint tissue damage.

Analysis of the function, expression, and subcellular distribution of human tristetraprolin.

Objective: The zinc-finger protein tristetraprolin (TTP) has been demonstrated to regulate tumor necrosis factor alpha (TNFalpha) messenger RNA (mRNA) instability in murine macrophages. We sought to develop a model system to characterize the effects of human TTP (hTTP) on TNFalpha 3'-untranslated region (3'-UTR)-mediated expression. We also generated a specific polyclonal antibody against hTTP that enabled the examination of the subcellular distribution of hTTP and its RNA binding in vivo.

Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1.

The therapeutic potential of placental growth factor (PlGF) and its receptor Flt1 in angiogenesis is poorly understood. Here, we report that PlGF stimulated angiogenesis and collateral growth in ischemic heart and limb with at least a comparable efficiency to vascular endothelial growth factor (VEGF). An antibody against Flt1 suppressed neovascularization in tumors and ischemic retina, and angiogenesis and inflammatory joint destruction in autoimmune arthritis.

Unilateral laminectomy for bilateral decompression of lumbar spinal stenosis: a prospective comparative study with conservatively treated patients.

The authors performed single- or multiple-level unilateral laminectomy to treat lumbar spinal stenosis in patients with mild to moderate leg pain and compared the results with those from patients treated with conservative therapy in a prospective study. This decompression technique produced a 68% rate of improvement compared with a 33% rate for conservatively treated patients. The surgical group exhibited significant and sustained improvement, whereas the functional and clinical status of the conservatively managed group had returned to baseline during the same period.

The distally based superficial sural flap: our experience in reconstructing the lower leg and foot.

The treatment of soft-tissue defects of the lower third of the leg and foot is often an awkward problem to tackle because of the frequent involvement of muscle, tendon, and bone, which is caused by the thinness and poor circulation of the skin covering them and by the small quantity of local tissue available for reconstruction. The authors present their experience with the use of sural flaps for the treatment of small- and medium-size defects of the distal region of the lower limb. The flap used was a distally based fasciocutaneous flap raised in the posterior region of the lower two thirds of the leg.