Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells

Butyrate acts as energy source for intestinal epithelial cells and as key mediator of several immune processes, modulating gene expression mainly through histone deacetylation inhibition. Thanks to these effects, butyrate has been proposed for the treatment of many intestinal diseases. Aim of this study was to investigate the effect of butyrate on the expression of a large series of target genes encoding proteins involved in pro-inflammatory pathways. We performed quantitative real-time-PCR analysis of the expression of 86 genes encoding proteins bearing to pro-inflammatory pathways, before and after butyrate exposure, in primary epithelial cells derived from human small intestine and colon. Butyrate significantly down-regulated the expression of genes involved in inflammatory response, among which nuclear factor kappa beta, interferon-gamma, Toll like 2 receptor and tumour necrosis factor-alpha. Further confirmations of these data, including studies at protein level, would support the use of butyrate as effective therapeutic strategy in intestinal inflammatory disorders

Physical activity regulates tnfα and il-6 expression to counteract inflammation in cystic fibrosis patients

Background: Cystic fibrosis (CF) is one of the most common inherited diseases. It is characterised by a severe decline in pulmonary function associated with metabolic perturbations and an increased production of inflammatory cytokines. The key role of physical activity (PA) in improving the health status of CF patients and reducing lung function decline has recently been demonstrated. This study evaluated interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) expression in two subgroups of CF patients classified based on PA. Methods: We selected 85 CF patients; half of them regularly undertook supervised PA in the three years leading up to the study and half of them were not physically active. Patients were analysed for serum IL-6 and TNFα levels using enzyme-linked immunosorbent assays. Results: We found that the expression levels of IL-6 and TNFα differed in terms of their regulation by PA. In particular, TNFα levels negatively correlated with FEV1% decrease/year and FEV1% decrease (p = 0.023 and p = 0.02, respectively), and positively correlated with serum fasting glucose (p = 0.019) in PA CF patients. In contrast, in the NPA subgroup, TNFα levels were positively correlated with IL-6 (p = 0.001) and negatively correlated with adiponectin (p = 0.000). In addition, multiple logistic regression analysis confirmed that PA is an independent modulator of the inflammatory state. Conclusions: PA modulates inflammatory processes in CF patients by regulating the secretion of pro-inflammatory cytokines and thus ameliorating lung function. Our data show that PA is a useful complementary strategy in the management of CF and that TNFα may be a marker of these effects of PA

m-Calpain is required for preimplantation embryonic development in mice

BACKGROUND: μ-calpain and m-calpain are ubiquitously expressed proteases implicated in cellular migration, cell cycle progression, degenerative processes and cell death. These heterodimeric enzymes are composed of distinct catalytic subunits, encoded by Capn1 (μ-calpain) or Capn2 (m-calpain), and a common regulatory subunit encoded by Capn4. Disruption of the mouse Capn4 gene abolished both μ-calpain and m-calpain activity, and resulted in embryonic lethality, thereby suggesting essential roles for one or both of these enzymes during mammalian embryogenesis. Disruption of the Capn1 gene produced viable, fertile mice implying that either m-calpain could compensate for the loss of μ-calpain, or that the loss of m-calpain was responsible for death of Capn4(-/- )mice. RESULTS: To distinguish between the alternatives described above, we deleted an essential coding region in the mouse Capn2 gene in embryonic stems cells and transmitted this mutant allele through the mouse germline. Breeding of heterozygous animals failed to produce homozygous mutant live offspring or implanted embryos. A nested PCR genotyping protocol was established, and homozygous preimplantation mutant embryos were detected at the morula but not at the blastocyts stage. CONCLUSION: We conclude that homozygous disruption of the Capn2 gene results in pre-implantation embryonic lethality between the morula and blastocyst stage. This establishes that μ-calpain and m-calpain have distinct functions, and that m-calpain is vital for development of the preimplantation murine embryo

From the Ketogenic Diet to the Mediterranean Diet: The Potential Dietary Therapy in Patients with Obesity after CoVID-19 Infection (Post CoVID Syndrome)

Purpose of review: This review primarily examines the evidence for areas of consensus and on-going uncertainty or controversy about diet and physical exercise approaches for in the post-CoVID. We propose an ideal dietary and physical activity approach that the patient with obesity should follow after CoVID-19 infection in order to reduce the clinical conditions associated with post-CoVID syndrome. Recent findings: The CoVID-19 disease pandemic, caused by the severe acute respiratory syndrome coronavirus-2, has spread all over the globe, infecting hundreds of millions of individuals and causing millions of death. It is also known to be is associated with several medical and psychological complications, especially in patients with obesity and weight-related disorders who in general pose a significant global public health problem, and in specific affected individuals are on a greater risk of developing poorer CoVID-19 clinical outcomes and experience a higher rate of mortality. Little is still known about the best nutritional approach to be adopted in this disease especially in the patients post-CoVID syndrome. Summary: To the best of our knowledge, no specific nutritional recommendations exist to manage in the patients post-CoVID syndrome. We report a presentation of nutritional therapeutic approach based on a ketogenic diet protocol followed by a transition to the Mediterranean diet in patients post-infection by CoVID, combined to a physical activity program to address conditions associated with post-CoVID syndrome

Positive-Tone, Aqueous-Developable, Polynorbornene Dielectric: Lithographic, and Dissolution Properties

ABSTRACT: A positive-tone, aqueous base soluble, polynorbornene (PNB) dielectric formulation has been developed. The photolithographic solubility switching mechanism is based on diazonaphthoquinone (DNQ) inhibition of PNB resin functionalized with pendent fluoroalcohol and carboxylic acid substituents. The optical contrast (at 365 nm) was found to be 2.3. The maximum height-towidth aspect ratio of developed line and space features was 3 : 2. The sensitivity, D 100 , of a formulation containing 20 pphr of DNQ photoactive compound (PAC) was calculated to be 408 mJ cm À2 . The effects of the PAC molecule structure on miscibility and dissolution of the photosensitive films in aqueous base developer were studied. The effect of the monomer composition of the PNB polymer on the dissolution rate of the formulated PNB resin was evaluated. A unique dissolution and swelling behavior was observed. The effect is attributed to a copolymer synthesized with two monomers each of which is susceptible to deprotonation in aqueous base. FTIR measurements showed that the pure PNBFA has a small percentage of free hydroxyl groups, which did not change appreciably by the addition of PAC to the mixture

Calpains mediate p53 activation and neuronal death evoked by DNA damage.

DNA damage is an initiator of neuronal death implicated in neuropathological conditions such as stroke. Previous evidence has shown that apoptotic death of embryonic cortical neurons treated with the DNA damaging agent camptothecin is dependent upon the tumor suppressor p53, an upstream death mediator, and more distal death effectors such as caspases. We show here that the calcium-regulated cysteine proteases, calpains, are activated during DNA damage induced by camptothecin treatment. Moreover, calpain deficiency, calpastatin expression, or pharmacological calpain inhibitors prevent the death of embryonic cortical neurons, indicating the important role of calpain in DNA damage-induced death. Calpain inhibition also significantly reduced and delayed the induction of p53. Consistent with the actions of calpains upstream of p53 and the proximal nature of p53 death signaling, calpain inhibition inhibited cytochrome c release and DEVD-AFC cleavage activity. Taken together, our results indicate that calpains are a key mediator of p53 induction and consequent caspase-dependent neuronal death due to DNA damage

BEVA primary care clinical guidelines: Wound Management in the Horse

Methods: Research questions were proposed by a panel of veterinarians, and developed into PICO format. Evidence in the veterinary literature was evaluated using the GRADE evidence-to-decision framework. Searches for human evidence summaries were conducted in the NICE, Cochrane and JBI databases. Final recommendations were based on both veterinary and human evidence. Results and recommendations: The research questions were categorised into three areas: A. Wound lavage and topical treatments; B. Wound debridement and closure; C. Therapeutics for wound healing. Three hundred and six veterinary publications were identified across thirteen different topics. Fourteen papers were assessed using the GRADE criteria. Twenty-five human evidence summaries were reviewed. The results were developed into recommendations: A. Wound lavage and topical treatments: (i) Tap water should be considered instead of saline for lavage; (ii) Povidone iodine lavage should be considered for contaminated wounds; (iii) Topical silver sulfadiazine may not be suitable for acute wounds; (iv) Optimal lavage pressures are around 13 psi. B. Wound debridement and closure: (i) Debridement pads should be considered for wound preparation; (ii) Larvae debridement should be considered in selected cases; (iii) Hydrosurgery should be considered in acute contaminated wounds. C. Therapeutics for wound healing: (i) Honey may reduce duration of some phases of wound healing. There was insufficient evidence to draw conclusions on the use of chemical debridement, therapeutic ultrasound, laser therapy, wound closure with staples compared to sutures, or identify optimal concentrations of antiseptic lavage solutions. Main limitations: Low quality evidence in veterinary literature; majority of recommendations were based on human evidence. Conclusions: These findings should be used to inform decision-making in equine primary care practice

Bulk heterojunction solar cells: the role of alkyl side chain on nanoscale morphology of sulfur overrich regioregular polythiophenes/fullerene blends.

Regioregular HH-TT poly(3,3’-thioalkylbithiophene)s bearing branched or linear alkyl side-chain substituents (PT2SR) have been synthesized and characterized in order to investigate their behavior, when used as electron donor components in blend with a fullerene derivative (PCBM) as electron acceptor, in air-processed photovoltaic solar cells with bulk heterojunction architecture. The optoelectronic characteristics, energy gap, nanoscale morphology and crystallinity of the blends (PT2SR/PCBM) were examined by UV–vis spectroscopy, cyclic voltammetry, Kelvin Probe Force Microscopy and X-ray diffraction. We demonstrate that thioalkyl substituents are able to influence the PCBM self-assembly and the morphology of the polymeric film, important parameters to maximize the efficiency of solar cell. In particular, the presence of chemical branching in the side chain of the sulfur overrich polythiophene backbone favors the formation of PCBM clusters, of size about 100±30 nm as confirmed by X-ray diffraction and KPFM measurements, and facilitates the intermixing between the donor and acceptor materials at the nanoscale level, thus determining a corresponding increase in device performance