RESUMO
Multiple pathogenic mechanisms are found in SARS-CoV2 systemic inflammation. Oxidative stress, altered proteolysis, hypercoagulation, and metabolic disorders are significant in virus-induced lesions. The study aimed to investigate the biochemical mechanism of virus-induced disorders and determine the biochemical features in SARS-CoV2-associated liver damage and intestine lesions. A retrospective case series of ninety-two patients diagnosed with COVID-19 pnemonia. The ACE, α1-proteinase inhibitor, trypsin-like proteinase, and elastase activity were measured. Nitrites level was detected in reaction with Griess reagent. The ELISA kit measured Troponin, C-peptide, leptin, adiponectin, PAR4, and neuropilin level. It was obtained an increase in ACE activity and nitrites ions content in SARS-CoV2 associated patients. The hyperglycemia and an increase in adipose tissue-derived hormones guided the virus-induced metabolic disorders. Proteolysis activation was revealed in SARS-CoV2 pneumonia patients. The found molecular event was accompanied by hyperglycemia induction. Multiorgan lesions manifest in in cardiac failure, which was detected in patients with ARDS. Moreover, high arterial blood pressure in patients with COVID-19 was associated with the hyperglycemia and increased ACE activity and NO ions level. Liver damage was specific for COVID-19-associated patients with severe ARDS and heart failure. Proteolysis overactivation resulting in vasoactive substances imbalance was detected in patients with the intestinal lesions. The obtained data shows the the neuropilin-dependent axis in damage prevalence in the intestine. Metabolic disorders resulting in the growth of adipose-derived tissue hormones, nitrites, and neuropilin levels was triggered by prolonged inflammation. So, the impaired metabolism and SARS-CoV2 associated hyperglycemia influence on SARS-CoV2 multiple mechanisms. Gastrointestinal manifestations in SARS-CoV2 infection was found to be related to various biochemical and molecular tools. ACE2 receptors axis is prevalent for liver damage, but NRP-1 protein (neuropilin), NO derivatives, and adipose tissue-derived hormones are essential for intestinal lesions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01089-x.
RESUMO
Autophagy plays a dual role in oncogenesis processes. On one hand, autophagy enhances the cell resistance to oncogenic factors, and on the other hand, it participates in the tumor progression. The aim of the study was to find the associations between the effectiveness of the FLOT regimen in resectable gastric cancers (GCs) with the key autophagy-related proteins. Materials and Methods: The study included 34 patients with morphologically verified gastric cancer. All patients had FLOT neoadjunvant chemotherapy (NACT) (fluorouracil, leucovorin, oxaliplatin, and docetaxel) followed by gastrectomy. The studied tissue material was the non-transformed and tumor tissues obtained during diagnostic video gastroscopy in patients before the start of the combined treatment and after surgical treatment, frozen after collection. The LC3B, mTOR, and AMPK expression was determined by real-time PCR. The content of the LC3B protein was determined by Western blotting analysis. Results: The mRNA level and the content of the LC3B protein were associated with the tumor stage and the presence of signet ring cells. The AMPK mRNA level was increased in patients with the T4N0-2M0 stage by 37.7 and 7.33 times, which was consequently compared with patients with the T2N0M0 and T3N0-1M0 stages. The opposite changes in the mTOR and AMPK in the GCs before anti-cancer therapy were noted. The tumor size and regional lymph node affections were associated with a decrease in the mTOR mRNA level. A decrease in the mTOR expression was accompanied by an increase in the AMPK expression in the GCs. The mTOR expression was reduced in patients with a cancer spreading; in contrast, AMPK grew with the tumor size. There was an increase in the LC3B expression, which can probably determine the response to therapy. An increase in LC3B mRNA before the start of treatment and the protein content in cancers after NACT with a decrease in therapy effectiveness was recorded. There was an increase in the protein level in patients with partial regression and stabilization by 3.65 and 5.78 times, respectively, when compared with patients with complete tumor regression was noted. Conclusions: The anticancer effectiveness in GCS is down to the LC3B, mTOR, and AMPK expression. These were found to be entire molecular targets affecting the cancer progression and metastasis as well as the NACT effectiveness.
