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Redox Biology Jun 2024Ferroptosis, a lipid peroxidation-driven cell death program kept in check by glutathione peroxidase 4 and endogenous redox cycles, promises access to novel strategies...
Ferroptosis, a lipid peroxidation-driven cell death program kept in check by glutathione peroxidase 4 and endogenous redox cycles, promises access to novel strategies for treating therapy-resistant cancers. Chlorido [N,N'-disalicylidene-1,2-phenylenediamine]iron (III) complexes (SCs) have potent anti-cancer properties by inducing ferroptosis, apoptosis, or necroptosis through still poorly understood molecular mechanisms. Here, we show that SCs preferentially induce ferroptosis over other cell death programs in triple-negative breast cancer cells (LC ≥ 0.07 μM) and are particularly effective against cell lines with acquired invasiveness, chemo- or radioresistance. Redox lipidomics reveals that initiation of cell death is associated with extensive (hydroper)oxidation of arachidonic acid and adrenic acid in membrane phospholipids, specifically phosphatidylethanolamines and phosphatidylinositols, with SCs outperforming established ferroptosis inducers. Mechanistically, SCs effectively catalyze one-electron transfer reactions, likely via a redox cycle involving the reduction of Fe(III) to Fe(II) species and reversible formation of oxo-bridged dimeric complexes, as supported by cyclic voltammetry. As a result, SCs can use hydrogen peroxide to generate organic radicals but not hydroxyl radicals and oxidize membrane phospholipids and (membrane-)protective factors such as NADPH, which is depleted from cells. We conclude that SCs catalyze specific redox reactions that drive membrane peroxidation while interfering with the ability of cells, including therapy-resistant cancer cells, to detoxify phospholipid hydroperoxides.
PubMed: 38955113
DOI: 10.1016/j.redox.2024.103257 -
Poultry Science Jun 2024Eggshell quality is a significant characteristic that influences consumer preferences. Eggshell translucency is a common defect in the appearance of eggshells, which are... (Review)
Review
Eggshell quality is a significant characteristic that influences consumer preferences. Eggshell translucency is a common defect in the appearance of eggshells, which are characterized by gray spots that are visible to the naked eye under natural light. The presence of various defects resulting from eggshell translucency has caused a decrease in consumer willingness to purchase eggs, leading to considerable economic losses in the egg industry. Although the impact of eggshell translucency on food safety, egg quality, and hatchability has been extensively investigated, the classification and causes of eggshell translucency remain unclear and lack a systematic summary. In recent studies, new interpretations of evaluation methods and causes of eggshell translucency have been proposed, along with numerous innovative solutions. Therefore, this paper aims to provide a comprehensive review of the evaluation methods, classification, causes, effects, and influencing factors of eggshell translucency and to summarize the treatments for translucent eggs. We believe that this review will serve as a valuable reference for researchers involved in the study of translucent eggs.
PubMed: 38954901
DOI: 10.1016/j.psj.2024.103983 -
Ultrasonics Sonochemistry Jun 2024Battery industry, one of the most crucial components of the modern world, relies heavily on lithium production, and brines from the spent battery materials is one of the...
Battery industry, one of the most crucial components of the modern world, relies heavily on lithium production, and brines from the spent battery materials is one of the most important sources to exploit lithium. A new ultrasonic assisted membrane processing is proposed for lithium separation simulated brine. The effects of membrane composition, feed concentration, and ultrasonic conditions on the lithium extraction efficiency have been explored. The composite membrane including polysulfone (PSF) as the support and 1-alkyl-3-methylimidazolium hexafluorophosphate and tributyl phosphate as ionic liquid membrane. A porous PVC membrane has been used for prevention of the ILM loss. The optimal ultrasonic frequency is approximately 250 kHz, which matches the bulk modulus of the membrane and enhances the separation efficiency. Higher frequencies and optimized amplitude and pulse cycle settings further improve the lithium flux and selectivity. Moreover, higher flux and selectivity are achieved when separating lithium from alkali metal chlorides at higher feed concentrations, ranging from 250 ppm to 1000 ppm. The mechanism of enhanced lithium extraction by ultrasonics is attributed to the combination of microbubble formation, cavitation, and heat generation, which disrupt the concentration gradient and facilitate lithium transport across the membrane.
PubMed: 38954863
DOI: 10.1016/j.ultsonch.2024.106974 -
PloS One 2024A number of seroprevalence studies in Zambia document the extent of spread of acute SARS-CoV-2 infection, yet knowledge gaps still exist on symptoms and conditions that...
Clinical characteristics and factors associated with long COVID among post-acute COVID-19 clinic patients in Zambia, August 2020 to January 2023: A cross-sectional and longitudinal study design.
INTRODUCTION
A number of seroprevalence studies in Zambia document the extent of spread of acute SARS-CoV-2 infection, yet knowledge gaps still exist on symptoms and conditions that continue or develop after acute COVID-19 (long COVID). This is an important gap given the estimated prevalence of long COVID in other African countries. We assessed factors associated with long COVID at the initial visit to a post-acute COVID-19 (PAC-19) clinic and longitudinally among a cohort of patients with ≥2 review visits.
METHODS
We implemented a cross-sectional and longitudinal analysis of PAC-19 clinic patients from Aug-2020 to Jan-2023. The study outcome was long COVID; defined as the presence of new, relapsing, or persistent COVID-19 symptoms that interfere with the ability to function at home or work. Explanatory variables were demographic and clinical characteristics of patients which included sex, age group, presence of new onset medical conditions, presence of pre-existing comorbidities, vaccination status and acute COVID-19 episode details. We fitted logistic and mixed effects regression models to assess for associated factors and considered statistical significance at p<0.05.
RESULTS
Out of a total 1,359 PAC-19 clinic patients in the cross-sectional analysis, 548 (40.3%) patients with ≥2 PAC-19 clinic visits were in the longitudinal analysis. Patients' median age was 53 (interquartile range [IQR]: 41-63) years, 919 (67.6%) were hospitalized for acute COVID-19, and of whom 686 (74.6%) had severe acute COVID-19. Overall, 377 (27.7%) PAC-19 clinic patients had long COVID. Patients with hospital length of stay ≥15 days (adjusted odds ratio [aOR]: 5.37; 95% confidence interval [95% CI]: 2.99-10.0), severe acute COVID-19 (aOR: 3.22; 95% CI: 1.68-6.73), and comorbidities (aOR:1.50; 95% CI: 1.02-2.21) had significantly higher chance of long COVID. Longitudinally, long COVID prevalence significantly (p<0.001) declined from 75.4% at the initial PAC-19 visit to 26.0% by the final visit. The median follow-up time was 7 (IQR: 4-12) weeks.
CONCLUSION
Factors associated with long COVID in Zambia were consistent both cross-sectionally at the initial visit to PAC-19 clinics and longitudinally across subsequent review visits. This highlights the importance of ongoing monitoring and tailored interventions for patients with comorbidities and severe COVID-19 to mitigate the long-term impacts of COVID-19.
Topics: Humans; Zambia; COVID-19; Male; Female; Cross-Sectional Studies; Longitudinal Studies; Adult; Middle Aged; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Aged; Young Adult; Adolescent; Comorbidity; Risk Factors; Prevalence
PubMed: 38954717
DOI: 10.1371/journal.pone.0306131 -
PloS One 2024Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory...
The impact of Astragaloside IV on the inflammatory response and gut microbiota in cases of acute lung injury is examined through the utilization of the PI3K/AKT/mTOR pathway.
OBJECTIVES
Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms.
METHODS
Different doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing.
RESULTS
AS-IV decreased the levels of TNF-α, IL-6, and IL-1β in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria.
CONCLUSION
AS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats.
Topics: Animals; Saponins; Triterpenes; Acute Lung Injury; TOR Serine-Threonine Kinases; Gastrointestinal Microbiome; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Signal Transduction; Rats; Male; Mice; Rats, Sprague-Dawley; Inflammation; Bronchoalveolar Lavage Fluid; Lung; Anti-Inflammatory Agents
PubMed: 38954702
DOI: 10.1371/journal.pone.0305058 -
PloS One 2024In the southeastern United States, wood ducks (Aix sponsa) have historically experienced interspecific brood parasitism (IBP) primarily from hooded mergansers...
In the southeastern United States, wood ducks (Aix sponsa) have historically experienced interspecific brood parasitism (IBP) primarily from hooded mergansers (Lophodytes cucullatus), but the recent northward expansion of black-bellied whistling-ducks (Dendrocygna autumnalis) has added a new complexity to these interactions. We monitored nest boxes in Louisiana to evaluate the influence IBP had on wood duck daily nest survival rate (after, DSR) and duckling recruitment. We monitored 1,295 wood duck nests from 2020-2023 and found 112 (8.7%) were parasitized by hooded mergansers and 148 (11.5%) by whistling-ducks. Parasitic egg-laying by hooded mergansers lowered wood duck DSR, while DSR for nests parasitized by whistling-ducks was comparable to clutches containing only wood duck eggs. We considered the wood duck capture histories of 2,465 marked female ducklings and 540 banded adult females to estimate a duckling recruitment probability for the entire study period. We recaptured 50 ducklings as adults; 6 (12.0%) hatched from clutches parasitized by hooded mergansers, 1 (2.0%) from a clutch parasitized by a whistling-duck, and 43 (86.0%) from clutches containing only wood duck eggs. The duckling recruitment probability was 0.039 (95% credible interval = 0.028, 0.051). Nest initiation date had a negative effect on recruitment, wherein most recruits hatched from nests initiated earlier in the season. Given only ~9% of wood duck nests contained hooded merganser eggs, we conclude IBP writ large had no detrimental effect on DSR at a population level. The lower DSR of clutches parasitized by hooded mergansers is potentially linked to a high abundance of early-season parasites that produce "dump nests" and these clutches are often abandoned without being incubated. Despite ongoing parasitism by hooded mergansers and the range expansion of whistling-ducks, wood duck productivity in Louisiana appears to be minimally affected by interspecific brood parasitism.
Topics: Animals; Ducks; Nesting Behavior; Female; Louisiana
PubMed: 38954676
DOI: 10.1371/journal.pone.0305899 -
European Thyroid Journal Jul 2024The aim of this study was to assess the clinical impact of hand-foot syndrome (HFS) during treatment with two multikinase inhibitors, sorafenib and lenvatinib, in a...
OBJECTIVE
The aim of this study was to assess the clinical impact of hand-foot syndrome (HFS) during treatment with two multikinase inhibitors, sorafenib and lenvatinib, in a large group of patients with advanced thyroid cancer. Moreover, we looked for possible associations between HFS occurrence and clinical and pathological features.
METHODS
We retrospectively evaluated 239 patients with advanced thyroid cancer: 165 treated with lenvatinib and 74 with sorafenib. Statistical analysis was performed to verify which features could be correlated with HFS development.
RESULTS
HFS was observed in 35/74 (47.4%) and in 43/165 (26.7%) patients treated with sorafenib or lenvatinib, respectively. The median latency from the drug beginning and HFS appearance was 27 days for sorafenib and 2.9 months for lenvatinib. G3/G4 toxicity was observed in 16/35 (45.7%) patients treated with sorafenib and only in 3/43 (7%) treated with lenvatinib. Drug dose reduction due to HFS was required in 19/74 (25.7%) and 3/165 (1.8%) patients treated with sorafenib and lenvatinib, respectively. HFS occurrence was significantly associated with a longer duration of therapy in both groups.
CONCLUSIONS
HFS was a frequent adverse event during both lenvatinib and sorafenib therapy, with a higher frequency and toxicity grade during sorafenib treatment. HFS was the most frequent reason for drug reduction or discontinuation in patient treated with sorafenib. Early diagnosis of HFS is important to allow early intervention, possibly in a multidisciplinary setting, and to avoid treatment discontinuation, which is highly relevant to obtain the maximum effectiveness of systemic therapy.
PubMed: 38954633
DOI: 10.1530/ETJ-24-0009 -
CEN Case Reports Jul 2024Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic hamartomatous gastrointestinal polyposis, hair loss, nail atrophy,...
Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic hamartomatous gastrointestinal polyposis, hair loss, nail atrophy, hyperpigmentation, and diarrhea. While the relationship between CCS and nephritis remains unclear, seven cases of nephritis complicated by CCS have been reported to date, all of which were membranous nephropathy (MN). A 57-year-old man presented with taste disturbance, hair loss, nail plate atrophy, skin pigmentation, and frequent diarrhea. Endoscopic findings showed multiple polyposis of the stomach and large intestine. Given the above, he was diagnosed with CCS. The symptoms gradually improved with prednisolone treatment, although urinary protein and hypoproteinemia appeared during the tapering of prednisolone. He was diagnosed with MN using a renal biopsy, and immunofluorescence microscopy with IgG subclass staining showed predominantly diffuse granular capillary wall staining of IgG4. The cause of secondary MN was not found, including malignant tumors. Nephrotic-range proteinuria persisted despite treatment with prednisolone and cyclosporine. Additional treatment with mizoribine resulted in incomplete remission type 1 of nephrotic syndrome, suggesting that mizoribine may be a treatment option for patients with CCS with steroid-resistant MN. Considering a high prevalence of hypoproteinemia due to chronic diarrhea and protein-losing enteropathy in patients with CCS, proteinuria might be overlooked; thus, follow-up urinalysis would be recommended in patients with CCS.
PubMed: 38954395
DOI: 10.1007/s13730-024-00908-9 -
Oncotarget Jul 2024Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). We previously reported that regorafenib...
Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status.
Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). We previously reported that regorafenib combined with a fluoropyrimidine can delay disease progression in clinical case reports of multidrug-resistant mCRC patients. We hypothesized that the combination of TAS102 and regorafenib may be active in CRC and other gastrointestinal (GI) cancers and may in the future provide a treatment option for patients with advanced GI cancer. We investigated the therapeutic effect of TAS102 in combination with regorafenib in preclinical studies employing cell culture, colonosphere assays that enrich for cancer stem cells, and . TAS102 in combination with regorafenib has synergistic activity against multiple GI cancers including colorectal and gastric cancer, but not liver cancer cells. TAS102 inhibits colonosphere formation and this effect is potentiated by regorafenib. anti-tumor effects of TAS102 plus regorafenib appear to be due to anti-proliferative effects, necrosis and angiogenesis inhibition. Growth inhibition by TAS102 plus regorafenib occurs in xenografted tumors regardless of p53, KRAS or BRAF mutations, although more potent tumor suppression was observed with wild-type p53. Regorafenib significantly inhibits TAS102-induced angiogenesis and microvessel density in xenografted tumors, as well inhibits TAS102-induced ERK1/2 activation regardless of RAS or BRAF status . TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms. The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.
Topics: Humans; Trifluridine; Phenylurea Compounds; Animals; Pyridines; Drug Synergism; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Neovascularization, Pathologic; Xenograft Model Antitumor Assays; Neoplastic Stem Cells; Gastrointestinal Neoplasms; Uracil; Mice; STAT3 Transcription Factor; Thymine; Drug Combinations; Cell Line, Tumor; Pyrrolidines; Mutation; Antineoplastic Combined Chemotherapy Protocols; MAP Kinase Signaling System; Signal Transduction; Cell Proliferation; Angiogenesis
PubMed: 38953895
DOI: 10.18632/oncotarget.28602 -
Aging Cell Jul 2024The dynamicity of the mitochondrial network is crucial for meeting the ever-changing metabolic and energy needs of the cell. Mitochondrial fission promotes the...
The dynamicity of the mitochondrial network is crucial for meeting the ever-changing metabolic and energy needs of the cell. Mitochondrial fission promotes the degradation and distribution of mitochondria, while mitochondrial fusion maintains mitochondrial function through the complementation of mitochondrial components. Previously, we have reported that mitochondrial networks are tubular, interconnected, and well-organized in young, healthy C. elegans, but become fragmented and disorganized with advancing age and in models of age-associated neurodegenerative disease. In this work, we examine the effects of increasing mitochondrial fission or mitochondrial fusion capacity by ubiquitously overexpressing the mitochondrial fission gene drp-1 or the mitochondrial fusion genes fzo-1 and eat-3, individually or in combination. We then measured mitochondrial function, mitochondrial network morphology, physiologic rates, stress resistance, and lifespan. Surprisingly, we found that overexpression of either mitochondrial fission or fusion machinery both resulted in an increase in mitochondrial fragmentation. Similarly, both mitochondrial fission and mitochondrial fusion overexpression strains have extended lifespans and increased stress resistance, which in the case of the mitochondrial fusion overexpression strains appears to be at least partially due to the upregulation of multiple pathways of cellular resilience in these strains. Overall, our work demonstrates that increasing the expression of mitochondrial fission or fusion genes extends lifespan and improves biological resilience without promoting the maintenance of a youthful mitochondrial network morphology. This work highlights the importance of the mitochondria for both resilience and longevity.
PubMed: 38953684
DOI: 10.1111/acel.14262