Multiple Roles of Peripheral Immune System in Modulating Ischemia/Hypoxia-Induced Neuroinflammation

Given combined efforts of neuroscience and immunology, increasing evidence has revealed the critical roles of the immune system in regulating homeostasis and disorders of the central nervous system (CNS). Microglia have long been considered as the only immune cell type in parenchyma, while at the interface between CNS and the peripheral (meninges, choroid plexus, and perivascular space), embryonically originated border-associated macrophages (BAMs) and multiple surveilling leukocytes capable of migrating into and out of the brain have been identified to function in the healthy brain. Hypoxia-induced neuroinflammation is the key pathological procedure that can be detected in healthy people at high altitude or in various neurodegenerative diseases, during which a very thin line between a beneficial response of the peripheral immune system in maintaining brain homeostasis and a pathological role in exacerbating neuroinflammation has been revealed. Here, we are going to focus on the role of the peripheral immune system and its crosstalk with CNS in the healthy brain and especially in hypobaric or ischemic hypoxia-associated neuroinflammation.

Heme Burden and Ensuing Mechanisms That Protect the Kidney: Insights from Bench and Bedside

With iron at its core, the tetrapyrrole heme ring is a cardinal prosthetic group made up of many proteins that participate in a wide array of cellular functions and metabolism. Once released, due to its pro-oxidant properties, free heme in sufficient amounts can result in injurious effects to the kidney and other organs. Heme oxygenase-1 (HO-1) has evolved to promptly attend to such injurious potential by facilitating degradation of heme into equimolar amounts of carbon monoxide, iron, and biliverdin. HO-1 induction is a beneficial response to tissue injury in diverse animal models of diseases, including those that affect the kidney. These protective attributes are mainly due to: (i) prompt degradation of heme leading to restraining potential hazardous effects of free heme, and (ii) generation of byproducts that along with induction of ferritin have proven beneficial in a number of pathological conditions. This review will focus on describing clinical aspects of some of the conditions with the unifying end-result of increased heme burden and will discuss the molecular mechanisms that ensue to protect the kidneys.

The use of feed supplements to reduce livestock greenhouse gas emissions: direct-fed microbials

This chapter aims to outline the strategy of using feed supplements for the reduction of greenhouse gas emissions (GHG) in ruminants, including methane (CH4), carbon dioxide and nitrous oxide, given that feed intake is an important variable in predicting these emissions. Focus will be given to direct-fed microbials, a term reserved for live microbes which can be supplemented to feed to elicit a beneficial response. The viability of such methods will also be analysed for their use in large scale on-farm operations.

Metabolic Support for Elderly, Severe COVID-19 Patients With Acute Respiratory Failure: A Case Series

Objectives Severe COVID-19 (SvC19) is a syndrome of acute lung injury, respiratory failure, cytokine storm, distributive shock, multi-system organ failure and high mortality. SvC19 disproportionately impacts the elderly, who are also at risk for micronutrient deficiency. After observing a beneficial response to micronutrient repletion (MR) in a 69 year-old male with SvC19, we hypothesized that nutritional deficiencies were linked to the pathogenesis and that correcting them could be beneficial. In this report we detail a case series of 18 older patients with SvC19 treated with MR. Methods All patients had SvC19 requiring mechanical ventilation, elevated levels of CRP, D-dimer and neutrophil to lymphocyte ratio. MR consisted of daily parenteral ascorbate, thiamine, pyridoxine and multivitamins, as well as daily ergocalciferol, zinc and carnitine via nasogastric tube. Results The average age was 63.3 years. Six patients were male, 12 female. Disease severity was comparable based on SOFA score. A partial response was observed in 10 of the 18 patients (55.5%). Six (33.3%) were able to wean off blood pressure support. Five (27.7%) had improvement in gas exchange. Four (22.2) were able to wean off ventilator support. Three patients (37.5%) showed improvement in renal dysfunction. Conclusions MR shows potential promise as an adjunctive treatment for severe COVID-19, particularly in older patients or those with chronic illness in whom nutritional deficiencies are more probable. Funding Sources None

Emerging understanding of apoptosis in mediating mesenchymal stem cell therapy

Mesenchymal stem cell transplantation (MSCT) has been recognized as a potent and promising approach to achieve immunomodulation and tissue regeneration, but the mechanisms of how MSCs exert therapeutic effects remain to be elucidated. Increasing evidence suggests that transplanted MSCs only briefly remain viable in recipients, after which they undergo apoptosis in the host circulation or in engrafted tissues. Intriguingly, apoptosis of infused MSCs has been revealed to be indispensable for their therapeutic efficacy, while recipient cells can also develop apoptosis as a beneficial response in restoring systemic and local tissue homeostasis. It is notable that apoptotic cells produce apoptotic extracellular vesicles (apoEVs), traditionally known as apoptotic bodies (apoBDs), which possess characterized miRnomes and proteomes that contribute to their specialized function and to intercellular communication. Importantly, it has been demonstrated that the impact of apoEVs is long-lasting in health and disease contexts, and they critically mediate the efficacy of MSCT. In this review, we summarize the emerging understanding of apoptosis in mediating MSCT, highlighting the potential of apoEVs as cell-free therapeutics.

A Link between Replicative Stress, Lamin Proteins, and Inflammation

Double-stranded breaks (DSB), the most toxic DNA lesions, are either a consequence of cellular metabolism, programmed as in during V(D)J recombination, or induced by anti-tumoral therapies or accidental genotoxic exposure. One origin of DSB sources is replicative stress, a major source of genome instability, especially when the integrity of the replication forks is not properly guaranteed. To complete stalled replication, restarting the fork requires complex molecular mechanisms, such as protection, remodeling, and processing. Recently, a link has been made between DNA damage accumulation and inflammation. Indeed, defects in DNA repair or in replication can lead to the release of DNA fragments in the cytosol. The recognition of this self-DNA by DNA sensors leads to the production of inflammatory factors. This beneficial response activating an innate immune response and destruction of cells bearing DNA damage may be considered as a novel part of DNA damage response. However, upon accumulation of DNA damage, a chronic inflammatory cellular microenvironment may lead to inflammatory pathologies, aging, and progression of tumor cells. Progress in understanding the molecular mechanisms of DNA damage repair, replication stress, and cytosolic DNA production would allow to propose new therapeutical strategies against cancer or inflammatory diseases associated with aging. In this review, we describe the mechanisms involved in DSB repair, the replicative stress management, and its consequences. We also focus on new emerging links between key components of the nuclear envelope, the lamins, and DNA repair, management of replicative stress, and inflammation.

Combination of Propranolol and Heated 4T1 Cells Elicits Beneficial Response Against Mouse Model of Breast Cancer

Background: Induction of Th1 responses against tumor antigens may be a useful strategy to control malignancy. In this respect, previous studies have shown that beta-adrenoreceptor antagonists can promote cellular immune responses. Objectives: This survey was done to evaluate the beneficiary of a new immunotherapy method against breast cancer made by mixing heated 4T1 cells and propranolol, as an adjuvant. Methods: Subcutaneously injected live 4T1 cells (1 × 104) were used to induce breast cancer in six to eight-week-old female Balb/c mice. when all mice had a palpable tumor, immunotherapy was dawned. Mice in the treatment groups were vaccinated, twice at a one-week interval, with the extract of heated 4T1(1 × 105) either alone or in combination with propranolol (6 mg/kg). Negative control mice received phosphate-buffered saline (PBS) as the same schedule. One-half of the mice were euthanized one week after the last vaccination to investigate the immune response profile. Other animals were kept until death occurred spontaneously. Results: Combined immunotherapy with propranolol and extract of heated 4T1 had synergistic effects, causing a more desirable survival curve and slower tumor growth when compared to other tumor-bearing mice receiving only heated 4T1 or PBS. Furthermore, combined immunotherapy significantly augmented the production of IFN-γ nitric oxide production, respiratory burst, and cytotoxicity of natural killer cells in the splenocyte culture of tumor-bearing mice. Conversely, combined immunotherapy significantly regressed the production of TGF-β and IL-10 in the splenocyte population compared to cytokine production by splenocytes from other groups. Conclusions: Combined heated 4T1 cells with propranolol promote beneficial outcomes in the animal model of breast cancer.

Kelebihan dan kekurangan penggunaan radiasi dosis rendah (Low Doses Radiation: advantages and disadvantages)

Objectives: To inform and discuss the benefits and harms of low dose radiation. Literature Review: Low dose radiation (LDR) was often used, including for services in the field of dentistry. Several studies have studied this for a long time but the results are still not conclusively agreed. Some researchers found a variety of side effects that are not beneficial to the body, but some found no association with the body damage caused by this, and even some found that LDR has beneficial effects on the body. Conclusion: low doses of radiation cause significant changes in the body, although this condition is met with an adaptive reaction which is considered a beneficial response by the body. Therefore, no matter how small the radiation is given, it will still have an impact on the body so it is better to be wise in its use.

Italian Ryegrass (Lolium multiflorum Lam.) Fiber Fraction Content and Dry Matter Digestibility Following Biostimulant Application against the Background of Varied Nitrogen Regime

An experiment was conducted to determine the effect of an application of biostimulants, against the background of varied nitrogen regime, on the share of neutral detergent fraction (NDF), acid detergent fraction (ADF), and acid detergent lignin (ADL) in the crude fiber fraction of Italian ryegrass as well as its digestibility. A field experiment was arranged as a randomized subblock design (split-plot) with three replicates at the Siedlce Experimental Unit of the University of Natural Sciences and Humanities in Poland in 2013. The following factors were examined: type of biostimulant: Algex, Tytanit, Asahi SL and a control; nitrogen application rate: 0 (control); 120 and 180 kg·ha−1. There were confirmed positive effects resulting from an application of biostimulants in Italian ryegrass cultivation. There was confirmed the assumed hypothesis that an application of both natural and synthetic biostimulants will make it possible to improve the feeding value of grasses by reducing the fiber fraction. Particular attention should be paid to the biostimulant Algex whose application in Italian ryegrass cultivation produced the most beneficial response in terms of the share of NDF, ADF, and ADL fractions, which resulted in the greatest increase in the plant dry matter digestibility. Increasing nitrogen rates significantly reduced the quantity of analyzed fiber fractions, and increased grass digestibility.