COVID-19: Immunohistochemical Analysis of TGF-β Signaling Pathways in Pulmonary Fibrosis

Acute respiratory distress syndrome (ARDS) followed by repair with lung remodeling is observed in COVID-19. These findings can lead to pulmonary terminal fibrosis, a form of irreversible sequelae. There is evidence that TGF-β is intimately involved in the fibrogenic process. When activated, TGF-β promotes the differentiation of fibroblasts into myofibroblasts and regulates the remodeling of the extracellular matrix (ECM). In this sense, the present study evaluated the histopathological features and immunohistochemical biomarkers (ACE-2, AKT-1, Caveolin-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-β1 tissue expression) involved in the TGF-β1 signaling pathways and pulmonary fibrosis. The study consisted of 24 paraffin lung samples from patients who died of COVID-19 (COVID-19 group), compared to 10 lung samples from patients who died of H1N1pdm09 (H1N1 group) and 11 lung samples from patients who died of different causes, with no lung injury (CONTROL group). In addition to the presence of alveolar septal fibrosis, diffuse alveolar damage (DAD) was found to be significantly increased in the COVID-19 group, associated with a higher density of Collagen I (mature) and III (immature). There was also a significant increase observed in the immunoexpression of tissue biomarkers ACE-2, AKT-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-β1 in the COVID-19 group. A significantly lower expression of Caveolin-1 was also found in this group. The results suggest the participation of TGF-β pathways in the development process of pulmonary fibrosis. Thus, it would be plausible to consider therapy with TGF-β inhibitors in those patients recovered from COVID-19 to mitigate a possible development of pulmonary fibrosis and its consequences for post-COVID-19 life quality.

Injury Rates in Female and Male Military Personnel: A Systematic Review and Meta-Analysis

Background: An effective military force is required to be agile, capable, efficient, and potent. Injuries to military personnel interrupt active-duty service and can detract from overall capability. These injuries are associated with a high individual and organizational burden, with lost work time and financial costs - all problematic for the ongoing functioning of a military force. Injury control strategies have therefore been described as force multipliers. Female personnel form an integral part of any modern defence force, but little research has examined their specific experiences of injury, to inform targeted injury control efforts. The aim of this review was to identify and synthesise findings from studies of injury rates and patterns in female military personnel, comparing them to those of male personnel.Methods: A systematic search was conducted for studies which compared injury rates between the sexes at any stage of military service, from basic training through to deployment. Databases searched included PUBMED, CINAHL and Medline through OVID. Methodological quality of eligible articles was assessed using the Critical Appraisal Skills Program (CASP), and AXIS tools and data were extracted, synthesized, and, where possible, underwent meta-analysis.Results: Of 2287 identified studies, a total of 25 studies were eligible and included. Methodological quality ranged from 60% up to a perfect score of 100%, with an average of 82% across all studies. Relative risks for injuries (reported as RR [95%CI]) to females when compared to males were 2.10 [1.89-2.33] during basic training, 1.70 [1.33–2.17] during officer training, and 1.23 [1.05-1.43] post initial training. After adjustment for differences between the sexes in average fitness levels (2-mile run time), there was no longer a significant difference in injury rates (adjusted RR: 0.95 [0.86-1.05]). Female personnel tended to make bigger improvements in their fitness during basic training than males and tended to report their injuries more frequently and sooner than males. Conclusion While this review found a higher rate of reported injuries in female military personnel when compared to male personnel, differences between the sexes in average fitness levels and injury reporting behaviours may largely explain this rate difference. The difference in rates of reported injuries was greatest during basic training, and reduced thereafter, possibly due in part to a reduced difference in fitness between the sexes or increased opportunity to self-determine workloads relative to fitness levels.

Acute Hyperthermia Syndromes

A high core body temperature is a medical emergency. Neuronal mitochondria and plasma membranes are thought to undergo protein changes at temperatures higher than 40°C, which lead to brain damage or dysfunction. In addition, the effects of hyperthermia on an already injured brain cause further injury. Control of fever is one of the important additional interventions necessary to control increased intracranial pressure and status epilepticus and to treat hypertensive surges in patients with sympathetic system overdrive.

Lycopene Aggravates Acute Gastric Injury Induced by Ethanol

Lycopene is an important natural red pigment with strong singlet oxygen and peroxide free radical quenching ability. Ethanol directly destroys the epithelial cells of gastric mucosa, causing oxidative damage and inflammation. To evaluate the effect of lycopene on the ethanol induced gastric injury, 112 adult male Kunming mice were randomly divided into normal control, lycopene control, gastric injury control, omeprazole (20 mg/kg) positive control, and lycopene experimental groups (at doses of 10, 50, 100, and 150 mg/kg body weight) in this study. The general and pathological evaluation, gastric secretion, as well as the levels of antioxidant and inflammatory factors were detected. In lycopene experimental groups, the amount of gastric juice were lower than that in the gastric injury control group; the levels of T-SOD, and the levels of MDA and inflammatory factors (MMP-9 and MCP-1) decreased. However, general and pathological evaluation of gastric tissues revealed that lycopene (especially at high doses) could aggravate acute gastric mucosal injury induced by ethanol. Therefore, lycopene (especially at high doses) aggravates acute gastric mucosal injury caused by ethanol, but this was not due to oxidative stress or inflammatory factors. In lycopene control group, the levels of MTL, T-SOD, and NO increased, but the levels of ALT and AST decreased, indicating that lycopene has a protective effect on the stomach and liver when ethanol wasn't taken. It reminds us that, when alcohol is consumed in large quantities, consumption of lycopene products should be carefully considered.

Trained Immunity in Anopheles gambiae: Antibacterial Immunity Is Enhanced by Priming via Sugar Meal Supplemented With a Single Gut Symbiotic Bacterial Strain

Mosquitoes have evolved an effective innate immune system. The mosquito gut accommodates various microbes, which play a crucial role in shaping the mosquito immune system during evolution. The resident bacteria in the gut microbiota play an essential role in priming basal immunity. In this study, we show that antibacterial immunity in Anopheles gambiae can be enhanced by priming via a sugar meal supplemented with bacteria. Serratia fonticola S1 and Enterobacter sp. Ag1 are gut bacteria in mosquitoes. The intrathoracic injection of the two bacteria can result in an acute hemocoelic infection in the naïve mosquitoes with mortality of ∼40% at 24 h post-infection. However, the Enterobacter orSerratia primed mosquitoes showed a better 24 h survival upon the bacterial challenge. The priming confers the protection with a certain degree of specificity, the Enterobacter primed mosquitoes had a better survival upon the Enterobacter but not Serratia challenge, and the Serratia primed mosquitoes had a better survival upon the Serratia but not Enterobacter challenge. To understand the priming-mediated immune enhancement, the transcriptomes were characterized in the mosquitoes of priming as well as priming plus challenges. The RNA-seq was conducted to profile 10 transcriptomes including three samples of priming conditions (native microbiota, Serratia priming, and Enterobacter priming), six samples of priming plus challenges with the two bacteria, and one sample of injury control. The three priming regimes resulted in distinctive transcriptomic profiles with about 60% of genes affected by both bacteria. Upon challenges, different primed mosquitoes displayed different transcriptomic patterns in response to different bacteria. When a primed cohort was challenged with a heterogenous bacterium, more responsive genes were observed than when challenged with a homogenous bacterium. As expected, many canonical immune genes were responsive to the priming and challenge, but much more non-immune genes with various functions were also responsive in the contexts, which implies that the prior priming triggers a delicately coordinated systemic regulation that results in an enhanced immunity against the subsequent challenge. Besides the participation of typical immune pathways, the transcriptome data suggest the involvement of lysosome and metabolism in the context. Overall, this study demonstrated a trained immunity via priming with bacteria in diet.

Low temperature exerts protective effects by inhibiting mitochondria-mediated apoptosis pathway following pressure injury to rat muscle

ABSTRACT Objective: We aimed to determine the effect of different low-temperature range interventions at different time-points in a rat model of pressure injury (PI) produced by Ischemia/Reperfusion (I/R) injury. Methods: Sprague-Dawley rats were randomly assigned to blank control, injury control, and temperature intervention groups. Rats in the injury control and temperature intervention groups (involving exposure to different temperature range at different time-points) were subjected to three cycles of I/R injury with 2-h ischemia and 0.5-h reperfusion to induce PI. Results: The muscle tissues exhibited degenerative changes after compression. Low temperature intervention of 16–18°C in the ischemia period resulted in the lowest degree of tissue damage and significantly decreased levels of Bcl-2-associated X protein (Bax), caspase-9, and caspase-3. Moreover, it resulted in the highest expression level of B-cell lymphoma 2 (Bcl-2) and lowest expression levels of Bax, caspase-9, and caspase-3 in muscle tissues among all intervention groups. Conclusion: Low-temperature intervention at 16–18°C during the ischemia period showed optimal effects on the expressions of apoptotic factors during the development of PI with I/R-induced tissue damage.

HISTOMORPHOMETRIC PARAMETERS OFTHE CARDIAC CONDUCTION SYSTEM AND THE MYOCARDIUM: CORRELATING RESULTS OF POSTMORTEM FORENSIC ANALYSIS ON ALCOHOLIC CARDIOMYOPATHY AND CORONARY HEART D

The article presents results of a study on the correlation of histomorphometric parameters of the heart in case of death from alcoholic cardiomyopathy (ACM), ischemic heart disease (IHD) and mechanical injury (control group) by the method of correlation analysis. The previous studies show that normally with age, the myocardium of the sinoatrial node (SAN) is most worn out and fibrosed. In case of IHD the His bundles are most worn out and fibrosed. In case of ACM, histomorphological changes are uniform in all areas of the myocardium. This indicator can be used in practice when providing differential diagnosis of the above-described types of pathology and causes of death. In addition, the results of our study confirm that myocardial lipomatosis is more typical of ACM, which increases its diagnostic value.