Remote Organ Research Articles

Single-cell analysis reveals the immune heterogeneity and interactions in lungs undergoing hepatic ischemia–reperfusion

Hepatic ischemia–reperfusion IR (HIR) is an unavoidable pathophysiological process during liver transplantation, resulting in systematic sterile inflammation and remote organ injury. Acute lung injury (ALI) is a serious complication after liver transplantation with high postoperative morbidity and mortality. However, the underlying mechanism is still unclear. To assess the phenotype and plasticity of various cell types in the lung tissue microenvironment after HIR at the single-cell level, single-cell RNA sequencing (scRNA-seq) was performed using the lungs from HIR-induced mice. In our results, we identified 23 cell types in the lungs after HIR and found that this highly complex ecosystem was formed by subpopulations of bone marrow-derived cells that signaled each other and mediated inflammatory responses in different states and different intervals. We described the unique transcriptional profiles of lung cell clusters and discovered two novel cell subtypes (Tspo+Endothelial cells and Vcan+ monocytes), as well as the endothelial cell-immune cell and immune cell-T cell clusters interactome. In addition, we found that S100 calcium binding protein (S100a8/a9), specifically and highly expressed in immune cell clusters of lung tissues and exhibited detrimental effects. Finally, the cellular landscape of the lung tissues after HIR was established, highlighting the heterogeneity and cellular interactions between major immune cells in HIR-induced lungs. Our findings provided new insights into the mechanisms of HIR-induced ALI and offered potential therapeutic target to prevent ALI after liver transplantation.

Numerical Simulation of a Lab-on-Chip for Dielectrophoretic Separation of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are cancer cells detached from tumors that enter the bloodstream with the rest of the blood cells before settling on remote organs and growing. CTCs play a major role as a target for cancer diagnosis. This study aims to propose and simulate a lab-on-chip (LOC) design that separates CTCs from white blood cells (WBCs) and blood platelets (PLTs) using low-voltage dielectrophoretic separation with high efficiency. The proposed design include two stages a passive and an active one cascaded in a compact package. Numerical simulations are performed on the COMSOL Multiphysics® software package to optimize the geometric parameters of the LOC, such as the width and length of the microchannel and the number of electrodes and their arrangements. Moreover, the effects of adjusting the applied voltage values as well as buffer inlet velocity are investigated. The proposed LOC design uses four electrodes at ±2 V to achieve 100% separation efficiency for the three cell types in simulation. The 919 µm × 440 µm LOC has a channel width of 40 µm. The inlet velocities for the blood-carrying cells and buffer are 134 and 850 µm/s, respectively. The proposed LOC can be used for the early detection of CTCs, which can be beneficial in cancer diagnosis and early treatment. In addition, it can be used in cancer prognosis, treatment monitoring and personalizing medicine.

The impacts of oral and gut microbiota on alveolar bone loss in periodontitis.

Periodontitis, a chronic infectious disease, primarily arises from infections and the invasion of periodontal pathogens. This condition is typified by alveolar bone loss resulting from host immune responses and inflammatory reactions. Periodontal pathogens trigger aberrant inflammatory reactions within periodontal tissues, thereby exacerbating the progression of periodontitis. Simultaneously, these pathogens and metabolites stimulate osteoclast differentiation, which leads to alveolar bone resorption. Moreover, a range of systemic diseases, including diabetes, postmenopausal osteoporosis, obesity and inflammatory bowel disease, can contribute to the development and progression of periodontitis. Many studies have underscored the pivotal role of gut microbiota in bone health through the gut-alveolar bone axis. The circulation may facilitate the transfer of gut pathogens or metabolites to distant alveolar bone, which in turn regulates bone homeostasis. Additionally, gut pathogens can elicit gut immune responses and direct immune cells to remote organs, potentially exacerbating periodontitis. This review summarizes the influence of oral microbiota on the development of periodontitis as well as the association between gut microbiota and periodontitis. By uncovering potential mechanisms of the gut-bone axis, this analysis provides novel insights for the targeted treatment of pathogenic bacteria in periodontitis.

The Potential Association of Human ABO Blood Group in Candida albicans Germination

Candidiasis is an infection caused by Candida spp., mostly Candida albicans. Infection with Candida spp. in immunocompetent individuals is often limited to the mouth, genital area or skin. However, patients who are immunocompromised due to infections or medications including corticosteroids or anticancer drugs are more susceptible to systemic candidiasis and candidemia. Upon C. albicans infections, the pathogenic yeasts enter the bloodstream and disseminate to the remote organs, leading to the formation of germ tube. Dimorphic adaptation is one of contributing virulent factors in C. albicans, which is responsible for disease pathogenesis and severity. However, little is known about whether differences among human ABO blood groups facilitate the development of C. albicans germ tube. Therefore, this study investigated the germ tube formation of C. albicans that grown in human serums from different ABO blood groups. Human pool serums varying ABO blood groups from healthy individuals were tested for C. albicans germ tube induction. After incubation for 2 h at 37 °C, the rate of germ tube formation at 15-min intervals was determined. Serum from human blood group A exhibited the highest rate of germ tube formation. Humans with blood group A exhibited the unique serum biochemical structure that possibly helps facilitate germ tube formation during C. albicans infection. HIGHLIGHTS The association of blood groups of Thais to germination and invasion of Candida albicans were more common in Thai people. This research study focused on changes in Candida albicans germination related to the blood group. Human with blood group type A exhibited the highest rate of germ tube formation. GRAPHICAL ABSTRACT

Interorgan communication networks in the kidney-lung axis.

The homeostasis and health of an organism depend on the coordinated interaction of specialized organs, which is regulated by interorgan communication networks of circulating soluble molecules and neuronal connections. Many diseases that seemingly affect one primary organ are really multiorgan diseases, with substantial secondary remote organ complications that underlie a large part of their morbidity and mortality. Acute kidney injury (AKI) frequently occurs in critically ill patients with multiorgan failure and is associated with high mortality, particularly when it occurs together with respiratory failure. Inflammatory lung lesions in patients with kidney failure that could be distinguished from pulmonary oedema due to volume overload were first reported in the 1930s, but have been largely overlooked in clinical settings. A series of studies over the past two decades have elucidated acute and chronic kidney-lung and lung-kidney interorgan communication networks involving various circulating inflammatory cytokines and chemokines, metabolites, uraemic toxins, immune cells and neuro-immune pathways. Further investigations are warranted to understand these clinical entities of high morbidity and mortality, and to develop effective treatments.

Impact of age on liver damage, inflammation, and molecular signaling pathways in response to femoral fracture and hemorrhage.

Trauma causes disability and mortality globally, leading to fractures and hemorrhagic shock. This can trigger an irregular inflammatory response that damages remote organs, including liver. Aging increases the susceptibility to dysregulated immune responses following trauma, raising the risk of organ damage, infections, and higher morbidity and mortality in elderly patients. This study investigates how aging affects liver inflammation and damage post-trauma. 24 male C57BL/6J mice were randomly divided into four groups. Twelve young (17-26 weeks) and 12 aged (64-72 weeks) mice were included. Mice further underwent either hemorrhagic shock (trauma/hemorrhage, TH), and femoral fracture (osteotomy) with external fixation (Fx) (THFx, n=6) or sham procedures (n=6). After 24 hours, mice were sacrificed. Liver injury and apoptosis were evaluated using hematoxylin-eosin staining and activated caspase-3 immunostaining. CXCL1 and infiltrating polymorphonuclear leukocytes (PMNL) in the liver were assessed by immunostaining, and concentrations of CXCL1, TNF, IL-1β, and IL-10 in the liver tissue were determined by ELISA. Gene expression of Tnf, Cxcl1, Il-1β, and Cxcl2 in the liver tissue was determined by qRT-PCR. Finally, western blot was used to determine protein expression levels of IκBα, Akt, and their phosphorylated forms. THFx caused liver damage and increased presence of active caspase-3-positive cells compared to the corresponding sham group. THFx aged group had more severe liver injury than the young group. CXCL1 and PMNL levels were significantly higher in both aged groups, and THFx caused a greater increase in CXCL and PMNL levels in aged compared to the young group. Pro-inflammatory TNF and IL-1β levels were elevated in aged groups, further intensified by THFx. Anti-inflammatory IL-10 levels were lower in aged groups. Tnf and Cxcl1 gene expression was enhanced in the aged sham group. Phosphorylation ratio of IκBα was significantly increased in the aged sham group versus young sham group. THFx-induced IκBα phosphorylation in the young group was significantly reduced in the aged THFx group. Akt phosphorylation was significantly reduced in the THFx aged group compared to the THFx young group. The findings indicate that aging may lead to increased vulnerability to liver injury and inflammation following trauma due to dysregulated immune responses.

A combination of 5/6-nephrectomy and unilateral ureteral obstruction model accelerates progression of remote organ fibrosis in chronic kidney disease.

Chronic kidney disease (CKD) involves progressive renal fibrosis, which gradually reduces kidney function and often causes various complications in extrarenal tissues. Therefore, we investigated fibrogenesis in extrarenal tissues (heart, liver, and lungs) in different experimental CKD models, such as the 5/6-nephrectomy (5/6 Nx), unilateral ureteral obstruction (UUO), and a combination (2/3 Nx + UUO). We evaluated the degree of fibrogenesis in kidneys and extrarenal tissues by histological analysis and quantification of fibrosis-related gene and protein expression. To elucidate the fibrosis mechanisms observed in 2/3 Nx + UUO mice, we evaluated the effect of indoxyl sulfate (IS), a typical uremic toxin accumulated in CKD, and transforming growth factor-β (TGF-β), a fibrosis-related factor, on fibrosis using human hepatoma (HepG2) and RAW264.7 cells. A significant decline in renal function was observed in the 5/6 Nx and 2/3 Nx + UUO models, whereas a significant increase in renal fibrosis was observed only in the obstructed kidneys. Notable amount of fibrosis was induced in the liver and heart in the 2/3 Nx + UUO model, with the induction of macrophage infiltration and increased tissue IS and TGF-β levels. In agreement with the results of in vivo experiments, co-stimulation with IS, TGF-β, and macrophage-conditioned medium increased the expression of fibrogenic genes in HepG2 cells. We demonstrated that the 2/3 Nx + UUO model induced both loss of renal function and renal fibrosis in the earlier stages, providing a novel CKD model that induces remote organ fibrosis in a shorter time.

Anti-inflammatory and anti-oxidant role of ursolic acid in cerulein-induced acute pancreatitis in rats.

Ursolic acid (UA) is found in many plants, and has been reported to have anti-protease, antioxidant, anti-inflammatory, antimicrobial, nephroprotective, hepatoprotective, and cardioprotective effects. The purpose of this study was to investigate the effects of ursolic acid in cerulein-induced acute pancreatitis (AP). Thirty-two Wistar albino rats were randomly assigned to 4 equal groups: Sham, acute pancreatitis, treatment, and ursolic acid group. Serum amylase levels in the AP and treatment groups were significantly higher than in the others (p < 0.05). In addition, serum IL-1β, IL-6, and TNF-α levels were significantly higher in the AP group in comparison with the treatment group. Although pancreatic tissue total oxidant activity in the AP and treatment groups was similar, pancreatic tissue total antioxidant capacity was significantly higher in the treatment group than in the AP group. Damage to the pancreas and remote organs in AP was observed to be reduced by UA. In addition, oxidative stress was observed to be decreased by the effect of UA.

Gut Microbiota and the Microvasculature.

The gut microbiota is increasingly recognized as an actuating variable shaping vascular development and endothelial cell function in the intestinal mucosa but also affecting the microvasculature of remote organs. In the small intestine, colonization with gut microbiota and subsequent activation of innate immune pathways promotes the development of intricate capillary networks and lacteals, influencing the integrity of the gut-vascular barrier as well as nutrient uptake. Since the liver yields most of its blood supply via the portal circulation, the hepatic microcirculation steadily encounters microbiota-derived patterns and active signaling metabolites that induce changes in the organization of the liver sinusoidal endothelium, influencing immune zonation of sinusoids and impacting on metabolic processes. In addition, microbiota-derived signals may affect the vasculature of distant organ systems such as the brain and the eye microvasculature. In recent years, this gut-resident microbial ecosystem was revealed to contribute to the development of several vascular disease phenotypes.

Gut microbial regulation of innate and adaptive immunity after traumatic brain injury.

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension, hypoxia, intracranial hypertension, and detrimental inflammation. However, the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems. Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease. A critical component of this axis is the microorganisms of the gut known as the gut microbiome. Changes in gut microbial populations in the setting of central nervous system disease, including traumatic brain injury, have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care. In this review article, we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury. We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

Evaluation of the therapeutic effects of oestradiol on the systemic inflammatory response and on lung injury caused by the occlusion of the proximal descending aorta in male rats.

Ischaemia and reperfusion-induced microvascular dysfunction is a serious problem encountered during a variety surgical procedures, leading to systemic inflammation and affecting remote organs, specially the lungs. 17β-Oestradiol reduces pulmonary repercussions from various acute lung injury forms. Here, we focused on the 17β-oestradiol therapeutic effects after aortic ischaemia and reperfusion (I/R) by evaluating lung inflammation. Twenty-four Wistar rats were submitted to I/R by insufflation of a 2-F catheter in thoracic aorta for 20 min. Reperfusion took 4 h and 17β-oestradiol (280 µg/kg, i.v.) was administered after 1 h of reperfusion. Sham-operated rats were controls. Bronchoalveolar lavage was performed and lung samples were prepared for histopathological analysis and tissue culture (explant). Interleukin (IL)-1β, IL-10 and tumour necrosis factor-α were quantified. After I/R, higher number of leukocytes in bronchoalveolar lavage were reduced by 17β-oestradiol. The treatment also decreased leukocytes in lung tissue. I/R increased lung myeloperoxidase expression, with reduction by 17β-oestradiol. Serum cytokine-induced neutrophil chemoattractant 1 and IL-1β increased after I/R and 17β-oestradiol decreased cytokine-induced neutrophil chemoattractant 1. I/R increased IL-1β and IL-10 in lung explants, reduced by 17β-oestradiol. Our results showed that 17β-oestradiol treatment performed in the period of reperfusion, modulated the systemic response and the lung repercussions of I/R by thoracic aortic occlusion. Thus, we can suggest that 17β-oestradiol might be a supplementary approach leading the lung deterioration after aortic clamping in surgical procedures.

Biomaterial based implants caused remote liver fatty deposition through activated blood-derived macrophages

Understanding the biocompatibility of biomaterials is a prerequisite for the prediction of its clinical application, and the present assessments mainly rely on in vitro cell culture and in situ histopathology. However, remote organs responses after biomaterials implantation is unclear. Here, by leveraging body-wide-transcriptomics data, we performed in-depth systems analysis of biomaterials – remote organs crosstalk after abdominal implantation of polypropylene and silk fibroin using a rodent model, demonstrating local implantation caused remote organs responses dominated by acute-phase responses, immune system responses and lipid metabolism disorders. Of note, liver function was specially disturbed, defined as hepatic lipid deposition. Combining flow cytometry analyses and liver monocyte recruitment inhibition experiments, we proved that blood derived monocyte-derived macrophages in the liver underlying the mechanism of abnormal lipid deposition induced by local biomaterials implantation. Moreover, from the perspective of temporality, the remote organs responses and liver lipid deposition of silk fibroin group faded away with biomaterial degradation and restored to normal at end, which highlighted its superiority of degradability. These findings were further indirectly evidenced by human blood biochemical ALT and AST examination from 141 clinical cases of hernia repair using silk fibroin mesh and polypropylene mesh. In conclusion, this study provided new insights on the crosstalk between local biomaterial implants and remote organs, which is of help for future selecting and evaluating biomaterial implants with the consideration of whole-body response.

Effect of valproic acid upon skeletal muscle subjected to prolonged tourniquet application

BackgroundValproic acid (VPA), a histone deacetylase inhibitor, has shown improved outcomes when used as a pharmaceutical intervention in animal studies of hemorrhage, septic shock, and combined injuries. This study was...

Ischemia/reperfusion-activated ferroptosis in the early stage triggers excessive inflammation to aggregate lung injury in rats.

Lung ischemia/reperfusion injury (LIRI) is a clinical syndrome of acute lung injury that occurs after lung transplantation or remote organ ischemia. Ferroptosis and inflammation are involved in the pathogenesis of LIRI according to the results of several studies on animal models. However, the interactive mechanisms between ferroptosis and inflammation contributing to LIRI remain unclear. HE staining and indicators of oxidative stress were used to evaluated the lung injury. The reactive oxygen species (ROS) level was examined by DHE staining. The quantitative Real-time PCR (qRT-PCR) and western blot analysis were employed to detect the level of inflammation and ferroptosis, and deferoxamine (DFO) was used to assess the importance of ferroptosis in LIRI and its effect on inflammation. In the present study, the link of ferroptosis with inflammation was evaluated at reperfusion 30-, 60- and 180-minute time points, respectively. As the results at reperfusion 30-minute point shown, the pro-ferroptotic indicators, especially cyclooxygenase (COX)-2 and acyl-CoA synthetase long-chain family member 4 (ACSL4), were upregulated while the anti-ferroptotic factors glutathione peroxidase 4 (GPX4), cystine-glumate antiporter (XCT) and ferritin heavy chain (FTH1) were downregulated. Meanwhile, the increased level of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α) and IL-1β were observed beginning at reperfusion 60-minute point but mostly activated at reperfusion 180-minute point. Furthermore, deferoxamine (DFO) was employed to block ferroptosis, which can alleviate lung injury. Expectedly, the survival rate of rats was increased and the lung injury was mitigated containing the improvement of type II alveolar cells ultrastructure and ROS production. In addition, at the reperfusion 180-minute point, the inflammation was observed to be dramatically inhibited after DFO administration as verified by IL-6, TNF-α and IL-1β detection. These findings suggest that ischemia/reperfusion-activated ferroptosis plays an important role as the trigger for inflammation to further deteriorate lung damages. Inhibiting ferroptosis may have therapeutic potential for LIRI in clinical practice.

Impaired microvascular circulation in distant organs following renal ischemia.

Mortality in acute kidney injury (AKI) patients remains very high, although very important advances in understanding the pathophysiology and in diagnosis and supportive care have been made. Most commonly, adverse outcomes are related to extra-renal organ dysfunction and failure. We and others have documented inflammation in remote organs as well as microvascular dysfunction in the kidney after renal ischemia. We hypothesized that abnormal microvascular flow in AKI extends to distant organs. To test this hypothesis, we employed intravital multiphoton fluorescence imaging in a well-characterized rat model of renal ischemia/reperfusion. Marked abnormalities in microvascular flow were seen in every organ evaluated, with decreases up to 46% observed 48 hours postischemia (as compared to sham surgery, p = 0.002). Decreased microvascular plasma flow was found in areas of erythrocyte aggregation and leukocyte adherence to endothelia. Intravital microscopy allowed the characterization of the erythrocyte formations as rouleaux that flowed as one-dimensional aggregates. Observed microvascular abnormalities were associated with significantly elevated fibrinogen levels. Plasma flow within capillaries as well as microthrombi, but not adherent leukocytes, were significantly improved by treatment with the platelet aggregation inhibitor dipyridamole. These microvascular defects may, in part, explain known distant organ dysfunction associated with renal ischemia. The results of these studies are relevant to human acute kidney injury.

Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis.

Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing (Gli1+) cells are a major source of activated fibroblasts in multiple organs, but the links between injury, inflammation, and Gli1+ cell expansion and tissue fibrosis remain incompletely understood. We demonstrated that leukocyte-derived tumor necrosis factor (TNF) promoted Gli1+ cell proliferation and cardiorenal fibrosis through induction and release of Indian Hedgehog (IHH) from renal epithelial cells. Using single-cell-resolution transcriptomic analysis, we identified an "inflammatory" proximal tubular epithelial (iPT) population contributing to TNF- and nuclear factor κB (NF-κB)-induced IHH production in vivo. TNF-induced Ubiquitin D (Ubd) expression was observed in human proximal tubular cells in vitro and during murine and human renal disease and aging. Studies using pharmacological and conditional genetic ablation of TNF-induced IHH signaling revealed that IHH activated canonical Hedgehog signaling in Gli1+ cells, which led to their activation, proliferation, and fibrosis within the injured and aging kidney and heart. These changes were inhibited in mice by Ihh deletion in Pax8-expressing cells or by pharmacological blockade of TNF, NF-κB, or Gli1 signaling. Increased amounts of circulating IHH were associated with loss of renal function and higher rates of cardiovascular disease in patients with chronic kidney disease. Thus, IHH connects leukocyte activation to Gli1+ cell expansion and represents a potential target for therapies to inhibit inflammation-induced fibrosis.

Conditional Cancer-Specific Survival for Inflammatory Breast Cancer: Analysis of SEER, 2010 to 2016

BackgroundConditional survival takes into account the time that has elapsed since diagnosis and may have additional informative value. Compared with the static traditional survival evaluation method, conditional survival predictions can be adapted to incorporate the dynamic changes during the disease and provide a more suitable way of identifying time-evolved prognoses. MethodsOf 3333 patients diagnosed with inflammatory breast cancer between 2010 and 2016 were extracted from the Surveillance, Epidemiology, and End Results database. The trend of the hazard rate over time was represented by the kernel density smoothing curve. The traditional cancer-specific survival (CSS) rate was estimated by the Kaplan-Meier method. Conditional CSS assessment was defined as the probability that a patient will survive y years given the x years who already survived after diagnosis, and the formula is as follows: CS(y)=CSS(x + y)/CSS(x). 3-year cancer-specific survival (CSS3) and 3-year conditional cancer-specific survival (CS3) were estimated. The Fine-Gray proportional subdistribution hazard model was constructed to screen for time-dependent risk factors associated with cancer-specific death. Subsequently, a nomogram was applied to predict a 5-year survival rate based on the number of years already survived. ResultsOf 3333 patients, the cancer-specific survival (CSS) rate decreased from 57% in the 4th year to 49% in the 6th year, while the comparable 3-year CS (CS3) rate improved from 65% in the first year to 76% in the third year. Overall, the CS3 rate was superior to actuarial cancer-specific survival, which was also found in subgroup analysis, especially in patients with high-risk characteristics. The Fine-Gray's model indicated that remote organ metastasis (M stage), lymph node metastasis (N stage), and surgery all significantly impacted the prognosis for cancer-specific survival. The Fine-Gray's model-based nomogram was constructed to predict 5-year cancer-specific survival immediately after diagnosis and given survival for 1, 2, 3, and 4 years after diagnosis. ConclusionHigh-risk patients had a significantly improved cancer-specific survival prognosis after surviving for 1 or more years after diagnosis with inflammatory breast cancer. The probability of reaching 5-year cancer-specific survival following diagnosis improves with each additional year survived. More effective follow-up is required for patients diagnosed at an advanced N stage, remote organ metastasis, or not received surgery. Additionally, a nomogram and web-based calculator may be helpful for patients with inflammatory breast cancer during follow-up counseling (https://ibccondsurv.shinyapps.io/dynnomapp/).

Polycystic testis in bull of Holstein Breed

Purpose : diagnosis of the disease and the subsequent surgical treatment of the Golstinsky breed bullshit in connection with a violation of the development of the testis. Materials and methods . The object of the study is the Golstein goby, which was born on a farm in Thuringia and then was contained in the general group (15 calves) on a deep straw litter. We carried out an early diagnosis of an animal disease aged 2 weeks, with a mass of 55 kg. During the clinical study, the condition of the calf was recorded as good, he actively took food, the clinical indicators were within normal limits, however, an increase in the volume of the scrotum that was inappropriate for its age was observed, and left -handed cryptorchidism was established. On the palpation of the scrotum, a slight soreness was noted, an increase in the right tested to 5 cm in length, 3 cm in width, the density of the shells of the testis and the fluctuation of the parenchyma. The left seed was not available for research due to its abdominal location. Since there was a rapid increase in the right seed, it was decided to carry out a unilateral castration of a bull to prevent the further development of the pathological process. Results . Castration was carried out with a bloody closed way on a firm ligature. The remote organ in the section did not have a clearly expressed parenchyma, but contained many cystic formations with transparent, liquid contents, in some cysts the contents were an admixture of blood. As a result of the surgical treatment of the bull, a pathologically changed testicist was removed, the second testis, which is abdominal, was left. To date, this disease is not fully studied and requires further thorough studies.

Oncogenic stress‐induced Netrin is a humoral signaling molecule that reprograms systemic metabolism in Drosophila

Cancer exerts pleiotropic, systemic effects on organisms, leading to health deterioration and eventually to organismal death. How cancer induces systemic effects on remote organs and the organism itself still remains elusive. Here we describe a role for NetrinB (NetB), a protein with a particularly well‐characterized role as a tissue‐level axon guidance cue, in mediating oncogenic stress‐induced organismal, metabolic reprogramming as a systemic humoral factor. In Drosophila, Ras‐induced dysplastic cells upregulate and secrete NetB. Inhibition of either NetB from the transformed tissue or its receptor in the fat body suppresses oncogenic stress‐induced organismal death. NetB from the dysplastic tissue remotely suppresses carnitine biosynthesis in the fat body, which is critical for acetyl‐CoA generation and systemic metabolism. Supplementation of carnitine or acetyl‐CoA ameliorates organismal health under oncogenic stress. This is the first identification, to our knowledge, of a role for the Netrin molecule, which has been studied extensively for its role within tissues, in humorally mediating systemic effects of local oncogenic stress on remote organs and organismal metabolism.

Yoghurt (LAB) as preventive method against COVID-19

SARS-COV-2 explores every possible vulnerability in human body and uses it against the host. To treat this SARS-COV-2 induced COVID-19, we should consider and target the multiple factors this virus is targeting and identify the drugs for usage in a strategical way. This approach can save the patients from severe state of illness and damage associated with this disease. COVID-19 has been associated with hyper inflammation [101-109] and delayed humoral immune responses [110-115]. Most of the complications with COVID-19 patients have been associated with early hypoxia, ARDS, pneumonia [116-122] and Acute Lung Injury [123-127]. Viral load has been found to be associated directly with incidence of lung injury/epithelial injury or remote organ injury in COVID-19 patients [128-133].