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The Journal of the Association of... Apr 2024A 21-year-old female patient presented to us with severe low back pain for 4 months. On examination, patient was afebrile, with severe pallor, and tenderness in both...
HISTORY AND EXAMINATION
A 21-year-old female patient presented to us with severe low back pain for 4 months. On examination, patient was afebrile, with severe pallor, and tenderness in both sacroiliac (SI) joints. Patient was being admitted and evaluated, and during the course of evaluation, developed severe headache, which was severe in intensity and associated with nausea and projectile vomiting. Initial investigations: An X-ray of the bilateral SI joints revealed inflammation, and the antinuclear antibody (ANA) turned out to be 4+ with pancytopenia and raised lactate dehydrogenase (LDH), but the liver function tests were normal. Rest of the rheumatological profile was unremarkable. During the course of the evaluation, she developed a severe headache, which, on imaging, showed presence of cerebral edema with chronic subdural hematoma, and a concomitant coagulopathy workup revealed evidence of disseminated intravascular coagulation (DIC).
DISCUSSION
Taking the whole picture into consideration, a malignant process in the body was suspected, and serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) were sent, all of which were raised. Validating the clinical clue was the bone marrow biopsy done for pancytopenia, which revealed malignant epithelial infiltration. A contrast-enhanced computed tomography (CECT) thorax and whole abdomen were done to find out the primary, which showed a neoplastic mass at the gastroesophageal junction along with bony metastases in the vertebrae and left adrenal. Tissue from the primary lesion was taken for histopathological examination (HPE) through upper gastrointestinal endoscopy. Although HPE revealed grade III poorly differentiated stomach adenocarcinoma, the patient had succumbed to the disease process by the time the diagnosis came to light.
CONCLUSION
In short, this case perfectly illustrates how solid organ malignancies might be a mimicker of multisystem disorders, thereby delaying diagnosis and worsening the prognosis even further.
Topics: Humans; Female; Pancytopenia; Disseminated Intravascular Coagulation; Young Adult; Autoimmunity
PubMed: 38881089
DOI: 10.59556/japi.72.0497 -
Journal of Pharmacological Sciences Aug 2024Elevation of the homocysteine concentration in the plasma called hyperhomocysteinemia (hHCY) during pregnancy causes a number of pre- and postnatal developmental...
Elevation of the homocysteine concentration in the plasma called hyperhomocysteinemia (hHCY) during pregnancy causes a number of pre- and postnatal developmental disorders. The aim of our study was to analyze the effects of HS donors -NaHS and N-acetylcysteine (NAC) on blood-brain barrier (BBB) permeability in rats with prenatal hHCY. In rats with mild hHCY BBB permeability assessed by Evans Blue extravasation in brain increased markedly throughout life. Administration of NaHS or NAC during pregnancy attenuated hHCY-associated damage and increased endogenous concentrations of sulfides in brain tissues. Acute application of dl-homocysteine thiolactone induced BBB leakage, which was prevented by the NMDA receptor antagonist MK-801 or HS donors. Rats with hHCY demonstrated high levels of NO metabolite - nitrites and proinflammatory cytokines (IL-1β, TNF-α, IL-6) in brain. Lactate dehydrogenase (LDH) activity in the serum was higher in rats with hHCY. Mitochondrial complex-I activity was lower in brain of hHCY rats. NaHS treatment during pregnancy restored levels of proinflammatory cytokines, nitrites and activity of the respiratory chain complex in brain as well as the LDH activity in serum. Our data suggest that HS has neuroprotective effects against prenatal hHCY-associated BBB disturbance providing a potential strategy for the prevention of developmental impairments in newborns.
Topics: Animals; Blood-Brain Barrier; Pregnancy; Hyperhomocysteinemia; Female; Hydrogen Sulfide; Neuroprotective Agents; Acetylcysteine; Cytokines; Homocysteine; Rats, Wistar; Sulfides; Rats; Male; Pregnancy Complications; Brain; L-Lactate Dehydrogenase; Permeability; Nitrites
PubMed: 38880547
DOI: 10.1016/j.jphs.2024.05.001 -
Cryobiology Jun 2024Current methods of storing explanted donor livers at 4°C in University of Wisconsin (UW) solution result in loss of graft function and ultimately leads to...
Current methods of storing explanted donor livers at 4°C in University of Wisconsin (UW) solution result in loss of graft function and ultimately leads to less-than-ideal outcomes post transplantation. Our lab has previously shown that supplementing UW solution with 35-kilodalton polyethylene glycol (PEG) has membrane stabilizing effects for cold stored primary rat hepatocytes in suspension. Expanding on past studies, we here investigate if PEG has the same beneficial effects in an adherent primary rat hepatocyte cold storage model. In addition, we investigated the extent of cold-induced apoptosis through treating cold-stored hepatocytes with pan caspase inhibitor emricasan. In parallel to storage at the current cold storage standard of 4°C, we investigated the effects of lowering the storage temperature to -4°C, at which the storage solution remains ice-free due to the supercooling phenomenon. We show the addition of 5% PEG to the storage medium significantly reduced the release of lactate dehydrogenase (LDH) in plated rat hepatocytes and a combinatorial treatment with emricasan maintains hepatocyte viability and morphology following recovery from cold storage. These results show that cold-stored hepatocytes undergo multiple mechanisms of cold-induced injury and that PEG and emricasan treatment in combination with supercooling may improve cell and organ preservation.
PubMed: 38880369
DOI: 10.1016/j.cryobiol.2024.104926 -
Journal of Thermal Biology Jun 2024The present research focuses on the seasonal changes in the energy content and metabolic patterns of red porgy (Pagrus pagrus) sampled in a fish farm in North Evoikos...
The present research focuses on the seasonal changes in the energy content and metabolic patterns of red porgy (Pagrus pagrus) sampled in a fish farm in North Evoikos Gulf (Greece). The study was designed in an effort to evaluate the influence of seasonality in several physiological feauteres of high commercial importance that may affect feed intake and growth. We determined glycogen, lipids and proteins levels, and cellular energy allocation (CEA) as a valuable marker of exposure to stress, which integrates available energy (Ea) and energy consumption (Ec). Metabolic patterns and aerobic oxidation potential were based on the determination of glucose transporter (GLU), carnitine transporter (CTP), L-lactate dehydrogenase (L-LDH), citrate synthase (CS), cytochrome C oxidase subunit IV isoform 1 (COX1) and 3-hydroxyacyl CoA dehydrogenase (HOAD) relative gene expression. To integrate metabolic patterns and gene expression, L-LDH, CS, COX and HOAD activities were also determined. For further estimation of biological stores oxidized during seasonal acclimatization, we determined the blood levels of glucose, lipids and lactate. The results indicated seasonal changes in energy content, different patterns in gene expression and reorganization of metabolic patterns during cool acclimatization with increased lipid oxidation. During warm acclimatization, however, energy consumption was mostly based on carbohydrates oxidation. The decrease of E and COX1 activity in the warm exposed heart seem to be consistent with the OCLTT hypothesis, suggesting that the heart may be one of the first organs to be limited during seasonal warming. Overall, this study has profiled changes in energetics and metabolic patterns occurring at annual temperatures at which P. pagrus is currently farmed, suggesting that this species is living at the upper edge of their thermal window, at least during summer.
PubMed: 38879912
DOI: 10.1016/j.jtherbio.2024.103894 -
Clinics (Sao Paulo, Brazil) 2024This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower...
OBJECTIVES
This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower extremities.
METHODS
An animal model of Deep Vein Thrombosis (DVT) and a hypoxic model of Human Umbilical Vein Endothelial Cells (HUVECs) treated with Cobalt (II) Chloride (CoCl) were developed. The expression levels of circUSP9X, microRNA-148b-3p (miR-148b-3p), and SRC Kinase Signaling Inhibitor 1 (SRCIN1) were quantified using quantitative reverse transcription Polymerase Chain Reaction and Western blot analysis. Cell cytotoxicity, viability, apoptosis, and inflammation in HUVECs were assessed via Lactate Dehydrogenase (LDH) assay, MTT assay, flow cytometry, Enzyme-Linked Immunosorbent Assay, and Western blot, respectively. Hematoxylin and Eosin staining were employed for histopathological examination of the venous tissues in the animal model. The interaction between circUSP9X, miR-148b-3p, and SRCIN1 was further explored through dual-luciferase reporter assays and RNA Immunoprecipitation experiments.
RESULTS
The present findings reveal a significant upregulation of circUSP9X and SRCIN1 and a concurrent downregulation of miR-148b-3p in DVT cases. Knockdown of circUSP9X or overexpression of miR-148b-3p ameliorated CoCl-induced apoptosis in HUVECs, reduced LDH release, enhanced cellular viability, and mitigated inflammation. Conversely, overexpression of circUSP9X intensified CoCl's cytotoxic effects. The effects of manipulating circUSP9X expression were counteracted by the corresponding modulation of miR-148b-3p and SRCIN1 levels. Additionally, circUSP9X knockdown effectively inhibited the formation of DVT in the mouse model. A competitive binding mechanism of circUSP9X for miR-148b-3p, modulating SRCIN1 expression, was identified.
CONCLUSION
circUSP9X promotes the formation of DVT through the regulation of the miR-148b-3p/SRCIN1 axis.
Topics: MicroRNAs; Animals; Venous Thrombosis; Human Umbilical Vein Endothelial Cells; Humans; Up-Regulation; Disease Models, Animal; RNA, Circular; Apoptosis; Male; Mice
PubMed: 38878321
DOI: 10.1016/j.clinsp.2024.100403 -
Chinese Medicine Jun 2024Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, a significant limitation in the clinical application of...
BACKGROUND
Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, a significant limitation in the clinical application of this widely used antineoplastic drug known for its efficacy. This study aimed to explore the effects and potential mechanisms underlying Lig's protective role against DOX-induced cardiotoxicity.
METHODS
C57BL/6 mice were treated with DOX. Cardiac function changes were observed by echocardiography. Cardiac structure changes were observed by HE and Masson staining. Immunofluorescence was applied to visualize the cardiomyocyte apoptosis. Western blotting was used to detect the expression levels of AMP-activated protein kinase (AMPK), sirtuin 3 (SIRT3), Caspase-3 and gasdermin E N-terminal fragment (GSDME-N). These experiments confirmed that Lig had an ameliorative effect on DOX-induced cardiotoxicity in mice.
RESULTS
The results demonstrated that Lig effectively countered myocardial oxidative stress by modulating intracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Lig reduced levels of creatine kinase (CK) and lactate dehydrogenase (LDH), while ameliorating histopathological changes and improving electrocardiogram profiles in vivo. Furthermore, the study revealed that Lig activated the AMPK/SIRT3 pathway, thereby enhancing mitochondrial function and attenuating myocardial cell apoptosis. In experiments with H9C2 cells treated with DOX, co-administration of the AMPK inhibitor compound C (CC) led to a significant increase in intracellular ROS levels. Lig intervention reversed these effects, along with the downregulation of GSDME-N, interleukin-1β (IL-1β), and interleukin-6 (IL-6), suggesting a potential role of Lig in mitigating Caspase-3/GSDME-mediated pyroptosis.
CONCLUSION
The findings of this study suggest that Lig effectively alleviates DOX-induced cardiotoxicity through the activation of the AMPK/SIRT3 pathway, thereby presenting itself as a natural product with therapeutic potential for preventing DOX-associated cardiotoxicity. This novel approach may pave the way for the development of alternative strategies in the clinical management of DOX-induced cardiac complications.
PubMed: 38877519
DOI: 10.1186/s13020-024-00955-5 -
Fish & Shellfish Immunology Jun 2024The impact of environmental factors on the health of the endangered Chinese sturgeon (Acipenser sinensis) and the potential hazards associated with sample collection for...
The impact of environmental factors on the health of the endangered Chinese sturgeon (Acipenser sinensis) and the potential hazards associated with sample collection for health monitoring pose urgent need to its conservation. In this study, Chinese sturgeons were selected from indoor and outdoor environments to evaluate metabolic and tissue damage indicators, along with a non-specific immune enzyme in fish mucus. Additionally, the microbiota of both water bodies and fish mucus were determined using 16S rRNA high-throughput sequencing. The correlation between the indicators and the microbiota was investigated, along with the measurement of multiple environmental factors. The results revealed significantly higher levels of two metabolic indicators, total protein (TP) and cortisol (COR) in indoor fish mucus compared to outdoor fish mucus (p < 0.05). The activities of acid phosphatase (ACP), alkaline phosphatase (ALP), creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were significantly higher in indoor fish, serving as indicators of tissue damage (p < 0.05). The activity of lysozyme (LZM) was significantly lower in indoor fish (p < 0.01). Biomarker analysis at the phylum and genus levels in outdoor samples revealed that microorganisms were primarily related to the catabolism of organic nutrients. In indoor environments, microorganisms displayed a broader spectrum of functions, including ecological niche establishment, host colonization, potential pathogenicity, and antagonism of pathogens. KEGG functional enrichment corroborated these findings. Dissolved oxygen (DO), electrical conductivity (EC), ammonia nitrogen (NH-N), turbidity (TU), and chemical oxygen demand (COD) exerted effects on outdoor microbiota. Temperature (TEMP), nitrate (NO), total phosphorus (TP), and total nitrogen (TN) influenced indoor microbiota. Changes in mucus indicators, microbial structure, and function in both environments were highly correlated with these factors. Our study provides novel insights into the health impacts of different environments on Chinese sturgeon using a non-invasive method.
PubMed: 38876409
DOI: 10.1016/j.fsi.2024.109700 -
Eastern Mediterranean Health Journal =... May 2024Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200...
BACKGROUND
Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200 children with suspected meningitis were admitted to hospital in Halabja Governorate, Iraq. No outbreak of meningitis had been reported previously in that region.
AIMS
To investigate the aetiology and epidemiology of meningitis among children in Halabja Governorate, Iraq, and expedite clinical management and prevention.
METHODOLOGY
Blood and cerebrospinal fluid specimens were collected from 197 children admitted to Halabja Paediatric and Maternity Teaching Hospital from 1 March to 1 July 2023 and analysed. The sample t-test was used to compare the haematological, serological and biochemical characteristics of the samples.
RESULTS
The majority (76.6%) of the children were aged 2-9 years and 54% were males. The clinical manifestations of the disease were fever (100.0%), headache (89.0%), vomiting (85.7%), and photophobia (72.4%); none of the children had convulsions. The mean values for both neutrophil count and C-reactive protein were statistically significantly raised (P < 0.05) and the red blood cells, white blood cells and neutrophil counts, and lactate dehydrogenase values were statistically significantly raised (P < 0.05). The causative organism was enterovirus (98.5%), with sporadic cases of streptococcal meningitis (1.5%). All the patients recovered fully.
CONCLUSION
The rapid diagnosis of the disease was crucial to the therapeutic and prevention control measures for the outbreak. Although it is still unclear how and where this outbreak started, contaminated drinking water and transmission among children in nurseries and schools are suspected. Further investigations are recommended to determine the source of the enterovirus and identify the virus species and serotypes.
Topics: Humans; Iraq; Child; Child, Preschool; Male; Disease Outbreaks; Female; Meningitis, Viral; Adolescent; Infant; Meningitis, Bacterial
PubMed: 38874294
DOI: 10.26719/2024.30.5.350 -
Oncology Reports Jul 20242',3',4'‑trihydroxyflavone (2‑D08), a SUMO E2 inhibitor, has several biological functions, including anticancer activity, but its effects on uterine leiomyosarcoma...
2',3',4'‑trihydroxyflavone (2‑D08), a SUMO E2 inhibitor, has several biological functions, including anticancer activity, but its effects on uterine leiomyosarcoma (Ut‑LMS) are unknown. The anticancer activity of 2‑D08 was explored in an model using SK‑LMS‑1 and SK‑UT‑1B cells (human Ut‑LMS cells). Treatment with 2‑D08 inhibited cell viability in a dose‑ and time‑dependent manner and significantly inhibited the colony‑forming ability of Ut‑LMS cells. In SK‑UT‑1B cells treated with 2‑D08, flow cytometric analysis revealed a slight increase in apoptotic rates, while cell cycle progression remained unaffected. Western blotting revealed elevated levels of RIP1, indicating induction of necrosis, but LC3B levels remained unchanged, suggesting no effect on autophagy. A lactate dehydrogenase (LDH) assay confirmed increased LDH release, further supporting the induction of apoptosis and necrosis by 2‑D08 in SK‑UT‑1B cells. 2‑D08‑induced production of reactive oxygen species and apoptosis progression were observed in SK‑LMS‑1 cells. Using Ki67 staining and bromodeoxyuridine assays, it was found that 2‑D08 suppressed proliferation in SK‑LMS‑1 cells, while treatment for 48 h led to cell‑cycle arrest. 2‑D08 upregulated p21 protein expression in SK‑LMS‑1 cells and promoted apoptosis through caspase‑3. Evaluation of α‑SM‑actin, calponin 1 and TAGLN expression indicated that 2‑D08 did not directly initiate smooth muscle phenotypic switching in SK‑LMS‑1 cells. Transcriptome analysis on 2‑D08‑treated SK‑LMS‑1 cells identified significant differences in gene expression and suggested that 2‑D08 modulates cell‑cycle‑ and apoptosis‑related pathways. The analysis identified several differentially expressed genes and significant enrichment for biological processes related to DNA replication and molecular functions associated with the apoptotic process. It was concluded that 2‑D08 exerts antitumor effects in Ut‑LMS cells by modulating multiple signaling pathways and that 2‑D08 may be a promising candidate for the treatment of human Ut‑LMS. The present study expanded and developed knowledge regarding Ut‑LMS management and indicated that 2‑D08 represents a notable finding in the exploration of fresh treatment options for such cancerous tumors.
Topics: Humans; Leiomyosarcoma; Female; Uterine Neoplasms; Cell Line, Tumor; Apoptosis; Cell Proliferation; Cell Survival; Gene Expression Regulation, Neoplastic; Reactive Oxygen Species; Signal Transduction; Flavones; Antineoplastic Agents; Cell Cycle; Autophagy
PubMed: 38874019
DOI: 10.3892/or.2024.8756 -
Molecular Medicine Reports Aug 2024Macrophage pyroptosis mediates vascular inflammation and atherosclerosis (AS). Hydrogen sulfide (H2S) exerts a protective role in preventing inflammation and AS....
Macrophage pyroptosis mediates vascular inflammation and atherosclerosis (AS). Hydrogen sulfide (H2S) exerts a protective role in preventing inflammation and AS. However, its molecular mechanisms of regulating the pyroptosis signaling pathway and inhibiting macrophage pyroptosis remain unexplored. The present study aimed to determine whether H2S mitigates macrophage pyroptosis by downregulating the pyroptosis signaling pathway and S‑sulfhydrating caspase‑1 under the stimulation of oxidized low‑density lipoprotein (ox‑LDL), a pro‑atherosclerotic factor. Macrophages derived from THP‑1 monocytes were pre‑treated using exogenous HS donors sodium hydrosulfide (NaHS) and D,L‑propargylglycine (PAG), a pharmacological inhibitor of endogenous HS‑producing enzymes, alone or in combination. Subsequently, cells were stimulated with ox‑LDL or the desulfhydration reagent dithiothreitol (DTT) in the presence or absence of NaHS and/or PAG. Following treatment, the levels of HS in THP‑1 derived macrophages were measured by a methylene blue colorimetric assay. The pyroptotic phenotype of THP‑1 cells was observed and evaluated by light microscopy, Hoechst 33342/propidium iodide fluorescent staining and lactate dehydrogenase (LDH) release assay. Caspase‑1 activity in THP‑1 cells was assayed by caspase‑1 activity assay kit. Immunofluorescence staining was used to assess the accumulation of active caspase‑1. Western blotting and ELISA were performed to determine the expression of pyroptosis‑specific markers (NLRP3, pro‑caspase‑1, caspase‑1, GSDMD and GSDMD‑N) in cells and the secretion of pyroptosis‑related cytokines [interleukin (IL)‑1β and IL‑18] in the cell‑free media, respectively. The S‑sulfhydration of pro‑caspase‑1 in cells was assessed using a biotin switch assay. ox‑LDL significantly induced macrophage pyroptosis by activating the pyroptosis signaling pathway. Inhibition of endogenous HS synthesis by PAG augmented the pro‑pyroptotic effects of ox‑LDL. Conversely, exogenous HS (NaHS) ameliorated ox‑LDL‑and ox‑LDL + PAG‑induced macrophage pyroptosis by suppressing the activation of the pyroptosis signaling pathway. Mechanistically, ox‑LDL and the DTT increased caspase‑1 activity and downstream events (IL‑1β and IL‑18 secretion) of the caspase‑1‑dependent pyroptosis pathway by reducing S‑sulfhydration of pro‑caspase‑1. Conversely, NaHS increased S‑sulfhydration of pro‑caspase‑1, reducing caspase‑1 activity and caspase‑1‑dependent macrophage pyroptosis. The present study demonstrated the molecular mechanism by which H2S ameliorates macrophage pyroptosis by suppressing the pyroptosis signaling pathway and S‑sulfhydration of pro‑caspase‑1, thereby suppressing the generation of active caspase-1 and activity of caspase-1.
Topics: Hydrogen Sulfide; Pyroptosis; Humans; Caspase 1; Macrophages; NLR Family, Pyrin Domain-Containing 3 Protein; Lipoproteins, LDL; Phosphate-Binding Proteins; THP-1 Cells; Intracellular Signaling Peptides and Proteins; Signal Transduction; Gasdermins; Alkynes; Glycine; Sulfides
PubMed: 38873985
DOI: 10.3892/mmr.2024.13259