Reactive Oxygen Radicals Research Articles

Defect-Rich Metastable MoS2 Promotes Macrophage Reprogramming in Breast Cancer: A Clinical Perspective.

Tumor-associated macrophages (TAMs) play a crucial function in solid tumor antigen clearance and immune suppression. Notably, 2D transitional metal dichalcogenides (i.e., molybdenum disulfide (MoS2) nanozymes) with enzyme-like activity are demonstrated in animal models for cancer immunotherapy. However, in situ engineering of TAMs polarization through sufficient accumulation of free radical reactive oxygen species for immunotherapy in clinical samples remains a significant challenge. In this study, defect-rich metastable MoS2 nanozymes, i.e., 1T2H-MoS2, are designed via reduction and phase transformation in molten sodium as a guided treatment for human breast cancer. The as-prepared 1T2H-MoS2 exhibited enhanced peroxidase-like activity (≈12-fold enhancement) than that of commercial MoS2, which is attributed to the charge redistribution and electronic state induced by the abundance of S vacancies. The 1T2H-MoS2 nanozyme can function as an extracellular hydroxyl radical generator, efficiently repolarizing TAMs into the M1-like phenotype and directly killing cancer cells. Moreover, the clinical feasibility of 1T2H-MoS2 is demonstrated via ex vivo therapeutic responses in human breast cancer samples. The apoptosis rate of cancer cells is 3.4 times greater than that of cells treated with chemotherapeutic drugs (i.e., doxorubicin).

Chronotropic Responses to GLP-1 Receptor Agonists and Sitagliptin in Atria From Diabetic Rats.

Type 2 diabetes mellitus increases the risk of cardiovascular diseases. Therefore, elucidation of the cardiovascular effects of antidiabetics is crucial. Incretin-based therapies are increasingly used for type 2 diabetes mellitus treatment as monotherapy and in combination. We aimed to study the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sitagliptin on beating rates in isolated atria from diabetic rats. The chronotropic responses to GLP-1 RAs and sitagliptin as monotherapy and in combinations with metformin, pioglitazone, and glimepiride in isolated atria from control and diabetic rats were determined. GLP-1 (7-36), GLP-1 (9-36), and exendin-4 (1-39) produced increases in beating rates in both control and diabetic rat atria. However, sitagliptin increased the beating frequency only in the diabetic group. Exendin (9-39), nitro- l -arginine methyl ester hydrochloride, and indomethacin blocked responses to GLP-1 RAs but not the response to sitagliptin. Glibenclamide, 4-aminopyridine, apamin, charybdotoxin, superoxide dismutase, and catalase incubations did not change responses to GLP-1 RAs and sitagliptin. GLP-1 RAs increase beating rates in isolated rat atrium through GLP-1 receptor, nitric oxide, and cyclooxygenase pathways but not potassium channels and reactive oxygen radicals.

Fabrication of losartan-loaded chitosan-cloaked dopamine nanoparticles for improving diabetic nephropathy via regulation of oxidative stress and blood glucose

Diabetic nephropathy (DN) is a significant problem for people with diabetes, and its progression is strongly associated with oxidative stress induced by high blood sugar levels (hyperglycemia). This study presents a novel type of losartan-loaded chitosan-cloaked dopamine nanoparticles (CSDLNPs). It can specifically aggregate in damaged kidneys, lower blood glucose levels, and ameliorate the damage caused by oxidative stress. CSDLNPs exhibit excellent dispersion physiological stability and sensitive release under an acidic pH milieu. Additionally, they have potent scavenging capabilities against a wide range of reactive nitrogen and oxygen radicals. Furthermore, in vitro, investigations validate that CSDLNPs exhibit superior biocompatibility, facilitate specific absorption in the HK-2 proximal tubule epithelial cell line, and effectively mitigate oxidative stress generated by high hyperglycemia. Following CSDLNPs treatment, DN exhibits a reduction in fasting blood glucose (FBG) levels and a restoration of urine and blood indices to levels close to normal. The H&E pathological staining results demonstrate that CSDLNPs effectively suppress collagen deposition, glycogen accumulation, and renal interstitium enlargement, indicating remarkable therapeutic efficacy. Furthermore, dopamine is a drug carrier and antioxidant without needing an external carrier, demonstrating superior biosafety and potential for translation to diabetic nephropathy.

S-Scheme heterojunction of Cs2SnBr6/C3N4 with interfacial electron exchange toward efficient photocatalytic NO abatement

Photocatalytic technology is of great significance in environmental purification due to its eco-friendly and cost-effective operations. However, low charge-transfer efficiency restricts the photocatalytic activity of the catalyst. Herein, we report Cs2SnBr6/C3N4 composite catalysts that exhibit a robust interfacial electron exchange thereby enhancing photocatalytic nitric oxide (NO) oxidation. A comprehensive study has demonstrated the S-scheme electron transfer mechanism. Benefiting from the interfacial internal electric field, the C-Br bond serves as a direct electron transfer channel, resulting in enhanced charge separation. Furthermore, the S-scheme heterojunction effectively traps high redox potential electrons and holes, leading to the production of abundant reactive oxygen radicals that enhance photocatalytic NO abatement. The NO removal rate of the Cs2SnBr6/C3N4 heterogeneous system can reach 86.8 %, which is approximately 3-fold and 18-fold that of pristine C3N4 and Cs2SnBr6, respectively. The comprehensive understanding of the electron transfer between heterojunction atomic interfaces will provide a novel perspective on efficient environmental photocatalysis.

Preparation of complex physicochemical synergistic inhibitors and study on inhibition of spontaneous combustion of coal

ABSTRACT To efficiently isolate oxygen and block free radical reactions， sodium alginate (SA), sodium polyacrylate (PAAS), attapulgite (ATP), and melatonin (MLT) were selected to develop an oxygen-insulating physicochemical synergistic inhibitor. The water loss experiment, EPR experiment, and programmed temperature rise experiment were used to characterize the performance of the inhibitor. The results show that the optimal ratio of the oxygen barrier physicochemical synergistic inhibitor is 2.5 wt% SA, 1.5 wt‰ PAAS, 9 wt% ATP, 6 wt% MLT, and 3 wt% CaCl2. In the oxygen-insulating physicochemical synergistic inhibitor, the MLT can react with oxidizing radicals in the coal to slow down the process of the oxidation reaction of the coal, and the SA gel can fill the pore space to prevent oxygen adsorption on the coal surface, the inhibition rate of the inhibitor reaches 70% at 120°C. Compared with the original coal, the CO concentration of the treated coal samples is reduced by 253.9ppm compared with that of the original coal, the generation rate is reduced by 1. 13 × 10−11 mol·cm−3·s−1, and the rate of oxygen consumption is reduced by 90. 65 × 10−11 mol·cm−3·s−1 at 120°C. The above results show that the oxygen-insulating physicochemical synergistic inhibitor developed in this paper can effectively improve the fire extinguishing efficiency is environmentally friendly and pollution-free, and has good application prospects.

Melanin nanoparticles scavenging reactive oxygen and nitrogen radicals for rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is a complex and chronic disease that often causes long-term pain and joint swelling in patients, and even causes joint deformity and dysfunction. The pathogenesis of this disease involves abnormal activity of the immune system, causing immune cells to attack the bodys joint tissues, which triggers an inflammatory response. During these inflammatory processes, the accumulation of reactive oxygen and nitrogen species (RONS) is considered to be one of the key factors that aggravate inflammation and damage joint tissues. To address this problem, we designed a method that takes advantage of the targeting properties of melanin nanoparticles. These nanoparticles have excellent biocompatibility, can remain stable in the body, and can be accurately targeted to the site of inflammation. In addition, these nanoparticles also have strong free radical scavenging ability, which can effectively neutralize excessive RONS, reduce the inflammatory response and weaken joint tissue damage. The promise of this treatment strategy is encouraging and offers new hope for patients with RA. By reducing inflammation, protecting joint tissue, and possibly even reversing the disease process to some extent, this melanin nanoparticle holds great promise.

Ca2+ Overload Decreased Cellular Viability in Magnetic Hyperthermia without a Macroscopic Temperature Rise.

Magnetic hyperthermia is a crucial medical engineering technique for treating diseases, which usually uses alternating magnetic fields (AMF) to interplay with magnetic substances to generate heat. Recently, it has been found that in some cases, there is no detectable temperature increment after applying an AMF, which caused corresponding effects surprisingly. The mechanisms involved in this phenomenon are not yet fully understood. In this study, we aimed to explore the role of Ca2+ overload in the magnetic hyperthermia effect without a perceptible temperature rise. A cellular system expressing the fusion proteins TRPV1 and ferritin was prepared. The application of an AMF (518 kHz, 16 kA/m) could induce the fusion protein to release a large amount of iron ions, which then participates in the production of massive reactive oxygen radicals (ROS). Both ROS and its induced lipid oxidation enticed the opening of ion channels, causing intracellular Ca2+ overload, which further led to decreased cellular viability. Taken together, Ca2+ overload triggered by elevated ROS and the induced oxidation of lipids contributes to the magnetic hyperthermia effect without a perceptible temperature rise. These findings would be beneficial for expanding the application of temperature-free magnetic hyperthermia, such as in cellular and neural regulation, design of new cancer treatment methods.

Photocatalytic Conversion of Methane to Ethanol at a Three-Phase Interface with Concentration-Matched Hydroxyl and Methyl Radicals.

The direct oxidation of CH4 to C2H5OH is attractive but challenging owing to the intricate processes involving carbon-chain growth and hydroxylation simultaneously. The inherent difficulty arises from the strong tendency of CH4 to overoxidize in the commonly used pressurized powder suspension systems rich in reactive oxygen radicals (ROR), which are specifically designed for CH4 concentration and activation. Meanwhile, the strong tendency of nucleophilic attack of potent ROR on the C-C bond of the resulting product C2H5OH ultimately leads to a higher selectivity for C1 oxygenates. This study addresses this multifaceted issue by designing a three-phase interface based on a hydrophilic floating Fe(III)-cross-linked macroporous alginate hydrogel film encapsulated with C3N4 [Fe(III)@ACN] to simultaneously enhance the accessibility of H2O and CH4 molecules to the active sites and species within the macroporous channel. The hydrophilic properties of Fe(III)@ACN allow the in situ production of H2O2 from C3N4 through the water oxidation reaction under irradiation. The concurrent photoinduced Fe(II) triggers Fenton reaction with H2O2 to produce •OH. The enhanced mass transfer of CH4 at the three-phase interface ensures the efficient formation of •CH3 by reacting with •OH, ultimately facilitating carbon-chain growth in the conversion pathway from CH4 to CH3OH and finally to C2H5OH with •CH3 and •OH present in comparable concentrations. Thus, the Fe(III)@ACN catalyst exhibits a remarkable 96% selectivity for alcohol, achieving a 90% selectivity for C2H5OH in the alcohol products. The C2H5OH production rate reaches 171.7 μmol g-1 h-1 without the need for precious-metal additive.

Anatomical, chemical and endophytic fungal diversity of a Qi-Nan clone of Aquilaria sinensis (Lour.) Spreng with different induction times.

Recently, some new Qi-Nan clones of Aquilaria sinensis (Lour.) Spreng which intensively produces high-quality agarwood have been identified and propagated through grafting techniques. Previous studies have primarily focused on ordinary A. sinensis and the differences in composition when compared to Qi-Nan and ordinary A. sinensis. There are few studies on the formation mechanism of Qi-Nan agarwood and the dynamic changes in components and endophytic fungi during the induction process. In this paper, the characteristics, chemical composition, and changes in endophytic fungi of Qi-Nan agarwood induced after 1 year, 2 years, and 3 years were studied, and Qi-Nan white wood was used as the control. The results showed that the yield of Qi-Nan agarwood continued to increase with the induction time over a period of 3 years, while the content of alcohol extract from Qi-Nan agarwood reached its peak at two years. During the formation of agarwood, starch and soluble sugars in xylem rays and interxylary phloem are consumed and reduced. Most of the oily substances in agarwood were filled in xylem ray cells and interxylary phloem, and a small amount was filled in xylem vessels. The main components of Qi-Nan agarwood are also chromones and sesquiterpenes. With an increasing induction time, the content of sesquiterpenes increased, while the content of chromones decreased. The most abundant chromones in Qi-Nan agarwood were 2-(2-Phenethyl) chromone, 2-[2-(3-Methoxy-4-hydroxyphenyl) ethyl] chromone, and2-[2-(4-Methoxyphenyl) ethyl] chromone. Significant differences were observed in the species of the endophytic fungi found in Qi-Nan agarwood at different induction times. A total of 4 phyla, 73 orders, and 448 genera were found in Qi-Nan agarwood dominated by Ascomycota and Basidiomycota. Different induction times had a significant effect on the diversity of the endophytic fungal community in Qi-Nan. After the induction of agarwood formation, the diversity of Qi-Nan endophytic fungi decreased. Correlation analysis showed that there was a significant positive correlation between endophytic fungi and the yield, alcohol extract content, sesquiterpene content, and chromone content of Qi-Nan agarwood, which indicated that endophytic fungi play a role in promoting the formation of Qi-Nan agarwood. Qi-Nan agarwood produced at different induction times exhibited strong antioxidant capacity. DPPH free radical scavenging activity and reactive oxygen species clearance activity were significantly positively correlated with the content of sesquiterpenes and chromones in Qi-Nan agarwood.

Mechanisms of ferroptosis in nonalcoholic fatty liver disease and therapeutic effects of traditional Chinese medicine: a review.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)), and lobular inflammation and hepatocyte damage (which characterize nonalcoholic steatohepatitis (NASH) are found in most patients). A subset of patients will gradually develop liver fibrosis, cirrhosis, and eventually hepatocellular carcinoma, which is a deadly disease that threatens human life worldwide. Ferroptosis, a novel nonapoptotic form of programmed cell death (PCD) characterized by iron-dependent accumulation of reactive oxygen radicals and lipid peroxides, is closely related to NAFLD. Traditional Chinese medicine (TCM) has unique advantages in the prevention and treatment of NAFLD due to its multicomponent, multipathway and multitarget characteristics. In this review, we discuss the effect of TCM on NAFLD by regulating ferroptosis, in order to provide reference for the further development and application of therapeutic drugs to treat NAFLD.

Phillyrin alleviates high glucose-induced oxidative stress and inflammation in HBZY-1 cells through inhibition of the PI3K/Akt signaling pathway.

Phillyrin, the major lignin compound of Forsythia suspense (Thunb.) Vahl, has been shown the effects of anti-inflammatory and antioxidant. Our study was aimed to explore the protective effect of phillyrin on glomerular mesangial cells (HBZY-1) and the potential mechanism. Cell viability, cytokine production, levels of reactive oxygen radicals (ROS), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as autophagy and apoptosis levels were determined to verify the mechanism of phillyrin on HBZY-1 cells. Our result indicated that phillyrin significantly inhibited HG-induced HBZY-1 proliferation by inhibiting Bcl-2 expression and upregulating Bad, cleaved caspase-3, and -9 expression. Also, phillyrin suppressed HG-induced mesangial extracellular matrix accumulation by inhibiting the expression of fibronectin and transforming growth factor-β1. Further, phillyrin inhibited oxidative stress and inflammation by decreasing ROS, MDA, TNF-α, IL-1β, and IL-6 contents and increasing SOD and GSH expression. Phillyrin also promoted autophagy by increasing LC3-II/LC3-I ratio and down-regulating p62 expression. Furthermore, WB assay showed that phillyrin inhibited oxidative stress caused by HG via activating Nrf2 signaling pathway, while attenuated proliferation and inflammation in HBZY-1 cells through inactivating PI3K/Akt/mTOR and NF-κB pathways. All results showed that phillyrin might be a promising therapeutic agent for the treatment of DN.

Ascorbic acid potentiates photodynamic inactivation mediated by octyl gallate and blue light for rapid eradication of planktonic bacteria and biofilms

This study reported for the first time that Ascorbic acid (AA) could appreciably boost the efficiency of Octyl gallate (OG)-mediated photodynamic inactivation (PDI) on Escherichia coli and Staphylococcus aureus in planktonic and biofilm states. The combination of OG (0.075 mM) and AA (200 mM) with 420 nm blue light (212 mW/cm2) led to a >6 Log killing within only 5 min for E. coli and S. aureus and rapid eradication of biofilms. The mechanism of action appears to be the generation of highly toxic hydroxyl radicals (•OH) via photochemical pathways. OG was exposed to BL irradiation to generate various reactive oxygen radicals (ROS) and the addition of AA could transform singlet oxygen (1O2) into hydrogen peroxide (H2O2), which could further react with AA to generate enormous •OH. These ROS jeopardized bacteria and biofilms by nonspecifically attacking various biomacromolecules. Overall, this PDI strategy provides a powerful microbiological decontamination modality to guarantee safe food products.

Generation and Radical-Radical Cross-Coupling of Alkenyloxy Radical.

Alkene-attached oxygen radicals are rarely used, as highly reactive oxygen radicals are incompatible with the alkene moiety. The direct radical-radical cross-coupling of O radicals is also challenging (limited to N-O bond formation) because of the lack of suitable persistent radical species. This study demonstrated the feasibility of using Breslow intermediate radical (BIR) as a persistent radical to capture unstable π-conjugated O radicals and allow the C-O radical-radical cross-coupling.

Synthesis of narrow-spectrum anti-mycobacterial molecules without effect on the diversity of gut microbiota in mice based on the structure of rifampicin

Rifampicin (RIF) is a broad-spectrum antimicrobial agent that is also a first-line drug for treating tuberculosis (TB). Based on the naphthyl ring structure of RIF this study synthesized 16 narrow-spectrum antimicrobial molecules that were specifically anti-Mycobacterium tuberculosis (Mtb). The most potent candidate was 2-((6-hydroxynaphthalen-2-yl) methylene) hydrazine-1-carbothioamide (compound 3c) with minimum inhibitory concentration (MIC) of 1 μg/mL against Mtb. Synergistic anti-Mtb test indicated that none of the combinations of 3c with the major anti-TB drugs are antagonistic. Consistent with RIF, compound 3c induced large amounts of reactive oxygen radicals (ROS) in the cells of Mtb. The killing kinetics of compound 3c and RIF are very similar. Furthermore, molecular docking showed that compound 3c was able to access the RIF binding pocket of the β subunit of Mtb RNA polymerase (RNAP). Experiments in mice showed that compound 3c increased the variety of intestinal flora in mice, while RIF significantly decreased the diversity of intestinal flora in mice. In addition, compound 3c is non-toxic to animal cells with a selection index (SI) much more than 10. The evidence from this study suggests that the further development of 3c could contribute to the development of novel drug for TB treatment.

A kidney-targeted chitosan-melanin nanoplatform for alleviating diabetic nephropathy through modulation of blood glucose and oxidative stress

Diabetic nephropathy (DN) is a serious complication in patients with diabetes, whose expansion process is closely related to oxidative stress caused by hyperglycemia. Herein, we report a chitosan-targeted dagliflozin-loaded melanin nanoparticle (CSMDNPs) that can selectively accumulate in injured kidneys, reduce blood glucose, and alleviate the oxidative stress-induced damage. CSMDNPs possess good dispersion and physiological stability, responsive release at acidic pH, and strong scavenging activities for various reactive oxygen and reactive nitrogen radicals. Moreover, in vitro experiments confirm that CSMDNPs have good biocompatibility, enable targeted uptake in NRK-52E renal tubular cells, and also well alleviate high glucose-induced oxidative stress. In the STZ-induced DN model, CSMDNPs exhibit high targeting distribution and retention in the damaged kidneys of DN mice according to photoacoustic imaging. At the end of CSMDNPs treatment, DN mice show a decrease in fasting blood glucose and a return to near-normal urine and blood indices. H&E, PAS, and masson pathological staining also indicates that CSMDNPs significantly inhibit the expansion of renal interstitium, glycogen, and collagen deposition, showing excellent therapeutic effects. In addition, melanin acts as both drug carrier and antioxidant without exogenous carrier introduction, exhibiting better biosafety and translational prospects.

Interaction of Human Gut Microflora with Commonly Consumed Herbs and Spices: A Review

Abstract: Herbs and spices are used since time memorable to transfuse color and add flavors to food. Their antibacterial properties also help preserve raw and cooked foods. Various diets composed of herbs and spices, as consistent with various researches, have been shown to influence life within the human digestive tract. This modulation forms the basis of various health effects that the herbs and spices and the microflora have on the human health. The intestinal microbiota is engaged in a critical function of promoting health, composed of favourable microbes (Lactobacillus and Bifidobacterium) and potentially harmful microorganisms (Salmonella thyphimurium and Escherichia coli). Spices and herbs make double oddities, i.e., inhibiting the proliferation of hazardous microbes while promoting favorable ones. The paper reviews the relevant manuscripts published in the past 20 years to understand the microbial modulation dynamics of herbs and spices. PubMed, Mendeley, SciELO, Scopus, Science Direct, and other peer-reviewed databases were accessed for the review. Microbial modulation is achieved by means of herbs and spices owing to the reduction of oxidative stress caused by reactive oxygen radicals, such as OHˉ, singlet O2, hydrogen peroxide, and superoxide radical, which leads to a threat to the intestinal microbiota. Spices and herbs have essential oils that serve as prebiotics, reducing the demand to impart artificial antioxidants, thus avoiding the associated health risks. Thus, the present review explores the mechanisms and underlying functions of herbs and spices in the human gut biome.

Overexpression of multidrug resistance-associated protein 1 protects against cardiotoxicity by augmenting the doxorubicin efflux from cardiomyocytes.

Doxorubicin is a commonly used anti-cancer drug used in treating a variety of malignancies. However, a major adverse effect is cardiotoxicity, which is dose dependent and can be either acute or chronic. Doxorubicin causes injury by DNA damage, the formation of free reactive oxygen radicals and induction of apoptosis. Our aim is to induce expression of the multidrug resistance-associated protein 1 (MRP1) in cardiomyocytes derived from human iPS cells (hiPSC-CM), to determine whether this will allow cells to effectively remove doxorubicin and confer cardioprotection. We generated a lentivirus vector encoding MRP1 (LV.MRP1) and validated its function in HEK293T cells and stem cell-derived cardiomyocytes (hiPSC-CM) by quantitative PCR and western blot analysis. The activity of the overexpressed MRP1 was also tested, by quantifying the amount of fluorescent dye exported from the cell by the transporter. We demonstrated reduced dye sequestration in cells overexpressing MRP1. Finally, we demonstrated that hiPSC-CM transduced with LV.MRP1 were protected against doxorubicin injury. In conclusion, we have shown that we can successfully overexpress MRP1 protein in hiPSC-CM, with functional transporter activity leading to protection against doxorubicin-induced toxicity.

Benzothiadiazole-functionalized Zr-MOF nanosheets enable visible-light mediated photocatalytic oxidation of sulfides in water

Ultrathin metal-organic frameworks (MOFs) nanosheets incorporating photochromic units are highly efficient heterogeneous photocatalysts, thanks to their highly exposed catalytic sites, short diffusion pathways, and efficient separation of photo-generated carriers. Herein, we report on the solvothermal synthesis of photoactive benzothiadiazole (BTz) functionalized Zr-MOF nanosheets (Zr-BTDB-NS), which are constructed from Zr12 nodes linked by nine BTDB2− (BTDB = 4,4′-(benzo[c][1,2,5]thiadiazole-4,7-diyl)dibenzoate) ligands. The Zr-BTDB-NS exhibited superior photocatalytic activity towards the aerobic oxidation of a broad range of sulfides to their corresponding sulfoxides under visible light irradiation in water at room temperature, even in a gram-scale. The Zr-BTDB-NS can be efficiently recycled and reused for seven cycles without a decrease in conversion or selectivity. Detailed mechanism studies revealed that the Zr-BTDB-NS generates singlet oxygen (1O2) and superoxide radical (O2–) reactive oxygen species under visible light irradiation, which are responsible for the oxidation of sulfides into their corresponding sulfoxides. The simplicity of the synthetic approach as well as the diversity of photoactive organic units hold great promise for designing ultrathin, water-stable, and photoactive Zr-MOF nanosheets. This work will also be of added value for selective photooxidation of sulfides under green and mild conditions.

The role of thiol/disulfide hemostasis in the diagnosis and severity prediction of acute pancreatitis

Objective: Reactive oxygen radicals are generated in the early stages of acute pancreatitis (AP) and are responsible for its progression. Thiol/disulfide homeostasis (TDH) is an important antioxidative mechanism. This study aimed to evaluate the role of TDH in the differential diagnosis of AP and predict its clinical severity.
 Methods: Patients admitted to the emergency department due to upper abdominal pain were evaluated. The study consisted of two groups: the AP group and the non-AP group (patients with diagnoses other than AP). The AP group was divided into mild and severe according to Acute physiology and chronic health evaluation II (APACHE-II) scores. TDH was measured with an automated assay from Erel et al. Statistical analyses were done with SPSS 16.0.
 Results: The results from 128 cases—58 in the AP group and 70 in the non-AP group—were evaluated. There was no difference in TDH parameters between the AP and non-AP groups. Among the AP subgroups, native thiol (sh) and total thiol (tt) were significantly lower in the severe AP group (sh: 313.9 μmol/L, 239.1 μmol/L; tt: 351.5 μmol/L, 303 μmo/L, respectively, in the mild and severe AP groups, P-value=0.006, P-value=0.013).
 Conclusion: TDH parameters change because of inflammatory processes in AP. Since this change does not occur for any specific reason, using TDH parameters for differential diagnosis of AP in patients with upper abdominal pain is not appropriate. However, in patients already diagnosed with AP, native and total thiol levels might be helpful in the prediction of clinical severity with a limited role.

Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID.

Pulmonary fibrosis, severe alveolitis, and the inability to restore alveolar epithelial architecture are primary causes of respiratory failure in fatal COVID-19 cases. However, the factors contributing to abnormal fibrosis in critically ill COVID-19 patients remain unclear. This study analyzed the histopathology of lung specimens from eight COVID-19 and six non-COVID-19 postmortems. We assessed the distribution and changes in extracellular matrix (ECM) proteins, including elastin and collagen, in lung alveoli through morphometric analyses. Our findings reveal the significant degradation of elastin fibers along the thin alveolar walls of the lung parenchyma, a process that precedes the onset of interstitial collagen deposition and widespread intra-alveolar fibrosis. Lungs with collapsed alveoli and organized fibrotic regions showed extensive fragmentation of elastin fibers, accompanied by alveolar epithelial cell death. Immunoblotting of lung autopsy tissue extracts confirmed elastin degradation. Importantly, we found that the loss of elastin was strongly correlated with the induction of neutrophil elastase (NE), a potent protease that degrades ECM. This study affirms the critical role of neutrophils and neutrophil enzymes in the pathogenesis of COVID-19. Consistently, we observed increased staining for peptidyl arginine deiminase, a marker for neutrophil extracellular trap release, and myeloperoxidase, an enzyme-generating reactive oxygen radical, indicating active neutrophil involvement in lung pathology. These findings place neutrophils and elastin degradation at the center of impaired alveolar function and argue that elastolysis and alveolitis trigger abnormal ECM repair and fibrosis in fatal COVID-19 cases. Importantly, this study has implications for severe COVID-19 complications, including long COVID and other chronic inflammatory and fibrotic disorders.