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1.
J Environ Sci (China) ; 151: 373-386, 2025 May.
Artigo em Inglês | MEDLINE | ID: mdl-39481946

RESUMO

The Pearl River Delta (PRD) region has been identified as a significant hotspot of wet ammonium deposition. However, the absence of long-term monitoring data in the area hinders the comprehension of the historical trends and changes in wet NH4+-N deposition in response to emissions, which interferes with the ability to make effective decisions. This study has analyzed the long-term trends of wet NH4+-N deposition flux and has quantified the effect of anthropogenic emissions and meteorological factors at a typical urban site and a typical forest site in the PRD region from 2009 to 2020. It revealed a significant decreasing trend in wet NH4+-N flux in both the typical urban and forest areas of the PRD region, at -6.2%/year (p < 0.001) and -3.3%/year (p < 0.001), respectively. Anthropogenic emissions are thought to have contributed 47%-57% of the wet NH4+-N deposition trend over the past 12 years compared to meteorological factors. Meteorological conditions dominated the inter-annual fluctuations in wet NH4+-N deposition with an absolute contribution of 46%-52%, while anthropogenic emissions change alone explained 10%-31%. NH3 emissions have the greatest impact on the urban area among anthropogenic emission factors, while SO2 emissions have the greatest impact on the forest area. Additionally, precipitation was identified as the primary meteorological driver for both sites. Our findings also imply that the benefits of NH3 emissions reductions might not immediately emerge due to interference from weather-related factors.


Assuntos
Poluentes Atmosféricos , Amônia , Monitoramento Ambiental , China , Amônia/análise , Poluentes Atmosféricos/análise , Rios/química , Efeitos Antropogênicos
2.
Clin Chim Acta ; 564: 119938, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39181293

RESUMO

OBJECTIVE: Delta bilirubin (albumin-covalently bound bilirubin) may provide important clinical utility in identifying impaired hepatic excretion of conjugated bilirubin, but it cannot be measured in real-time for diagnostic purposes in clinical laboratories. METHODS: A total of 210 samples were collected, and their delta bilirubin levels were measured four times using high-performance liquid chromatography. Data collected included age, sex, diagnosis code, delta bilirubin, total bilirubin, direct bilirubin, total protein, albumin, globulin, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, hemoglobin, serum hemolysis value, hemolysis index, icterus value (Iv), icterus index (Ii), lipemia value (Lv), and lipemia index. To conduct feature selection and identify the optimal combination of variables, linear regression machine learning was performed 1,000 times. RESULTS: The selected variables were total bilirubin, direct bilirubin, total protein, albumin, hemoglobin, Iv, Ii, and Lv. The best predictive performance for high delta bilirubin concentrations was achieved with the combination of albumin-direct bilirubin-hemoglobin-Iv-Lv. The final equation composed of these variables was as follows: delta bilirubin = 0.35 × Iv + 0.05 × Lv - 0.23 × direct bilirubin - 0.05 × hemoglobin - 0.04 × albumin + 0.10. CONCLUSION: The equation established in this study is practical and can be easily applied in real-time in clinical laboratories.


Assuntos
Bilirrubina , Aprendizado de Máquina , Bilirrubina/sangue , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Adulto Jovem , Criança , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Pré-Escolar , Lactente
3.
J Environ Sci (China) ; 149: 314-329, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181645

RESUMO

Extensive spatiotemporal analyses of long-trend surface ozone in the Yangtze River Delta (YRD) region and its meteorology-related and emission-related have not been systematically analyzed. In this study, by using 8-year-long (2015-2022) surface ozone observation data, we attempted to reveal the variation of multiple timescale components using the Kolmogorov-Zurbenko filter, and the effects of meteorology and emissions were quantitatively isolated using multiple linear regression with meteorological variables. The results showed that the short-term, seasonal, and long-term components accounted for daily maximum 8-hr average O3 (O3-8 hr) concentration, 46.4%, 45.9%, and 1.0%, respectively. The meteorological impacts account for an average of 71.8% of O3-8 hr, and the YRD's eastern and northern sections are meteorology-sensitive areas. Based on statistical analysis technology with empirical orthogonal function, the contribution of meteorology, local emission, and transport in the long-term component of O3-8 hr were 0.21%, 0.12%, and 0.6%, respectively. The spatiotemporal analysis indicated that a distinct decreasing spatial pattern could be observed from coastal cities towards the northwest, influenced by the monsoon and synoptic conditions. The central urban agglomeration north and south of the YRD was particularly susceptible to local pollution. Among the cities studied, Shanghai, Anqing, and Xuancheng, located at similar latitudes, were significantly impacted by atmospheric transmission-the contribution of Shanghai, the maximum accounting for 3.6%.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Ozônio , China , Ozônio/análise , Poluentes Atmosféricos/análise , Rios/química , Estações do Ano , Meteorologia , Poluição do Ar/estatística & dados numéricos , Poluição do Ar/análise
4.
J Environ Sci (China) ; 150: 202-217, 2025 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39306396

RESUMO

This study focuses on the spatiotemporal distribution, urban-rural variations, and driving factors of ammonia Vertical Column Densities (VCDs) in China's Yangtze River Delta region (YRD) from 2008 to 2020. Utilizing data from the Infrared Atmospheric Sounding Interferometer (IASI), Generalized Additive Models (GAM), and the GEOS-Chem chemical transport model, we observed a significant increase of NH3 VCDs in the YRD between 2014 and 2020. The spatial distribution analysis revealed higher NH3 concentrations in the northern part of the YRD region, primarily due to lower precipitation, alkaline soil, and intensive agricultural activities. NH3 VCDs in the YRD region increased significantly (65.18%) from 2008 to 2020. The highest growth rate occurs in the summer, with an annual average growth rate of 7.2% during the period from 2014 to 2020. Agricultural emissions dominated NH3 VCDs during spring and summer, with high concentrations primarily located in the agricultural areas adjacent to densely populated urban zones. Regions within several large urban areas have been discovered to exhibit relatively stable variations in NH3 VCDs. The rise in NH3 VCDs within the YRD region was primarily driven by the reduction of acidic gases like SO2, as emphasized by GAM modeling and sensitivity tests using the GEOS-Chem model. The concentration changes of acidic gases contribute to over 80% of the interannual variations in NH3 VCDs. This emphasizes the crucial role of environmental policies targeting the reduction of these acidic gases. Effective emission control is urgent to mitigate environmental hazards and secondary particulate matter, especially in the northern YRD.


Assuntos
Poluentes Atmosféricos , Amônia , Monitoramento Ambiental , Rios , China , Amônia/análise , Poluentes Atmosféricos/análise , Rios/química , Agricultura , Análise Espaço-Temporal , Estações do Ano
5.
Front Cell Dev Biol ; 12: 1490040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39493348

RESUMO

In this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and posterior foregut by treatment with FGF7, SANT1, LDN193189, PdBU, and retinoic acid (RA). The subsequent endocrine generation and directed SC-delta cell induction is achieved by a combined treatment of the FGF7 with FGF2 during stage 4 and 5, together with RA, XXI, ALK5 inhibitor II, SANT1, Betacellulin and LDN193189. The planar cultivation is converted to a suspended system after stage 5, allowing cells to aggregate into delta cell-containing spheroids. The differentiation takes approximately 4-5 weeks for delta cell generation and an additional 1-2 weeks for cell expansion and evaluation. We believe that this amenable and simplified protocol can provide a stable source of SC-delta cells from efficient differentiation, facilitating further investigation of the physiological role of delta cells as well as refinement of islet cell therapeutic strategies.

6.
Heliyon ; 10(20): e39281, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39497956

RESUMO

Caragobius urolepis has a wide range of distribution, from brackish to freshwater water, ranging from India to the Philippines and Fiji, including the Vietnamese Mekong Delta (VMD), where it lives mainly in the coastal regions and plays a vital role in food supply. Our preliminary observation showed that its population tended to decline, but little is known about this species. This study, therefore, was conducted to provide data on the ovarian structure, spawning pattern and season, length at first maturity, and batch fecundity of this fish. The study of 306 specimens caught with trawl nets from April 2022 to March 2023 in two coastal areas of VMD-Dong Hai, Bac Lieu (DHBL), and Dam Doi, Ca Mau (DDCM)-showed that this goby spawned more than once because the oocytes in stage IV ovary showed different stages of development. It could release eggs monthly during a 12-month study, with a peak in July-September since stage IV ovaries were found monthly during the study period and the GSI exhibited a high value in July-September. The fish length at first maturity and batch fecundity varied with the site, as they were 18.8 cm and 3,757-9,187 (6,142 ± 707 SE eggs/female) in DDCM and 20.5 cm and 3,760-11,118 (5,634 ± 750 SE eggs/female) in DHBL. The findings provide valuable foundations for exploiting their resources and serve as a basis for studying artificial reproduction. It is suggested to avoid catching these fish species during the breeding season to ensure sustainable exploitation in the future.

7.
Mar Pollut Bull ; 209(Pt B): 117184, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39486206

RESUMO

Identifying the baseline status and the timing of ecosystem disturbances are essential for restoration programs. The historical bioaccumulation of heavy metals was assessed from an 80-cm-long core from the Manzala Lagoon (Nile Delta). The heavy metal concentrations increased slightly upward and peaked around 1964, after the completion of Aswan High Dam. The metal concentrations of shells are 2-3 times less than those of bulk sediment. The topmost sediments are enriched in Cd, Cu, and Pb above USEPA. Sediment type and sediment grain size have a minor effect on the heavy metal concentration in mollusk shells, suggesting a priority over bulk sediments. Although correlated, the shells of the grazer gastropod Melanoides tuberculata have the highest concentration of all metals relative to the suspension-feeder bivalves Cerastoderma glaucum and Saccostrea cuculata. This was attributed to the influences of the eco-physiological traits, which exert a similar influence on the bioaccumulation process of all metals.

8.
Heliyon ; 10(19): e38974, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39435117

RESUMO

Freshwater scarcity is a critical issue in Vietnam, particularly in the Mekong Delta, a densely populated region with an agriculture-based economy. This scarcity is largely driven by saltwater intrusion during the dry season, severely affecting both agriculture and the local economy. In response, advanced desalination technologies have been proposed. In this study, we investigated the use of cyclopentane (CP), a liquid guest molecule, and 1,1,1,2-tetrafluoroethane (R134a), a gaseous guest molecule, as hydrate formers to desalinate saline water from the Mekong Delta. This study aimed to evaluate and compare the freshwater recovery efficiencies of these hydrate formers and assess the potential of hydrate technology for practical application in the region. We performed thermodynamic and kinetic investigations on sodium chloride solutions (1.0-3.5 wt%), representing the salinity levels of seawater in the Mekong Delta, to establish a laboratory-scale desalination system. The results showed a consistent thermodynamic trend: the higher concentration of samples leads to the longer time of hydrate formation to achieve the conversion of water into hydrates exceeding 60 %. Additionally, the CP and R134a hydrate structures were characterized using Raman spectroscopy, which revealed significant changes in the water peak and C-H band signal during the hydrate formation process. After a single-stage hydrate treatment using CP and R134a, the removal efficiencies for ions and total dissolved solids in saline water samples from the Mekong Delta exceeded 75 % and 70 %, respectively. These findings serve as a reference for developing a larger-scale hydrate-based desalination technology to address the challenges of saltwater intrusion in the Mekong Delta region.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39438262

RESUMO

Abstract: During the SARS-CoV-2 Delta (B.1.617.2) variant outbreak, from August to October 2021 in the Australian Capital Territory (ACT), the number of new cases 'in the community for part of their infectious period' was publicly reported daily. We describe the stratification tool used during the outbreak to determine presumptive risk of community transmission from cases, and present the results of a contemporaneous validation of each case's risk against their onward transmission detected by routine surveillance. After case interview, epidemiologists identified the most likely source of infection for each new case and used the stratification tool to classify the case as either no, low, or high risk of community transmission. Each case notified between 12 August and 14 September 2021 was matched to its recipient case(s) to determine how well the tool predicted transmission risk. Household transmissions were excluded. Of the 530 notified cases stratified, 159 (29.3%) were cases who transmitted to a recipient case. Of the 59 cases who were the source of community transmission, 66% (38/59) were undertaking high-risk activities not associated with permitted essential work at the time. Only six source cases stratified as low risk or no risk transmitted SARS-CoV-2 to those outside their own household. The tool was essential in the rapid determination of community transmission risk in the ACT, and validation of the tool against detected onward transmission provided evidence for the effectiveness of public health restrictions. In the early stages of outbreaks of diseases for which transmissibility has not yet been established, the validation of such a stratification tool relies on high quality case investigation data, but may help to understand transmission dynamics and to inform interventions.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/transmissão , Território da Capital Australiana/epidemiologia , Medição de Risco , Surtos de Doenças , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/transmissão , Infecções Comunitárias Adquiridas/virologia , Idoso
10.
Microbiol Mol Biol Rev ; : e0001424, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39440957

RESUMO

SUMMARYHepatitis B virus (HBV) is an important human pathogen that chronically infects approximately 250 million people in the world, resulting in ~1 million deaths annually. This virus is a hepatotropic virus and can cause severe liver diseases including cirrhosis and hepatocellular carcinoma. The entry of HBV into hepatocytes is initiated by the interaction of its envelope proteins with its receptors. This is followed by the delivery of the viral nucleocapsid to the nucleus for the release of its genomic DNA and the transcription of viral RNAs. The assembly of the viral capsid particles may then take place in the nucleus or the cytoplasm and may involve cellular membranes. This is followed by the egress of the virus from infected cells. In recent years, significant research progresses had been made toward understanding the entry, the assembly, and the egress of HBV particles. In this review, we discuss the molecular pathways of these processes and compare them with those used by hepatitis delta virus and hepatitis C virus , two other hepatotropic viruses that are also enveloped. The understanding of these processes will help us to understand how HBV replicates and causes diseases, which will help to improve the treatments for HBV patients.

11.
Influenza Other Respir Viruses ; 18(10): e70019, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39440811

RESUMO

BACKGROUND: The global pandemic caused by SARS-CoV-2 has underlined the significance of strict genomic surveillance to track virus evolution and the possible emergence of new variants, particularly in densely populated countries like Bangladesh. This study outlines a strategic framework of genomic surveillance to track the evolution of the virus in Bangladesh between June 2021 and December 2022 through the National SARS-CoV-2 Variant Surveillance (NSVS) program involving collaboration across 4 major institutes and 13 hospitals nationwide. METHODS: We aimed to capture the variants of SARS-CoV-2 throughout the country utilizing standardized procedures, modern sequencing technology, and stringent quality control, promoting data accuracy and the timely detection of new variants of concern. We sequenced over 2200 genomes, documenting the prevalence of the Delta variant initially, followed by the emergence of Omicron variants BA.1, BA.2, BA.5, and XBB, each affecting transmission rates and vaccine efficacy differently. RESULTS: The clinical manifestations of the variants differed, with some symptoms occurring more frequently in Delta cases and vice versa. Vaccinated individuals were more affected by Omicron cases compared to Delta cases. These variants were responsible for two major COVID-19 waves in the country, each with significant clinical effects. Phylogenetic analyses placed the local SARS-CoV-2 variants within a global context, indicating the Delta variant likely entered from India and Omicron from Europe. CONCLUSION: This research highlights the significance of collaborative surveillance strategies for guiding public health choices and the critical role of genomic analysis in monitoring virus evolution, shaping targeted pandemic responses. Bangladesh's contributions significantly enhance global insight into COVID-19's genomic evolution.


Assuntos
COVID-19 , Genoma Viral , SARS-CoV-2 , Bangladesh/epidemiologia , Humanos , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , Genoma Viral/genética , Genômica , Filogenia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade
12.
Front Pharmacol ; 15: 1439536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39444618

RESUMO

Background: Pichia pastoris-secreted delta sleep inducing peptide and crossing the blood-brain barrier peptides (DSIP-CBBBP) fusion peptides holds significant promise for its potential sleep-enhancing and neurotransmitter balancing effects. This study investigates these properties using a p-chlorophenylalanine (PCPA) -induced insomnia model in mice, an approach akin to traditional methods evaluating sleep-promoting activities in fusion peptides. Aim of the study: The research aims to elucidate the sleep-promoting mechanism of DSIP-CBBBP, exploring its impact on neurotransmitter levels and sleep regulation, and to analyze its composition and structure. Materials and methods: Using a PCPA-induced insomnia mouse model, the study evaluates the sleep-promoting effects of DSIP-CBBBP. The peptide's influence on neurotransmitters such as 5-HT, glutamate, dopamine, and melatonin is assessed. The functions of DSIP-CBBBP are characterized using biochemical and animal insomnia-induced behavior tests and compared without CBBBP. Results: DSIP-CBBBP demonstrates a capacity to modulate neurotransmitter levels, indicated by changes in 5-HT, glutamate, DA, and melatonin. DSIP-CBBBP shows a better restorative effect than DSIP on neurotransmitter imbalance and the potential to enhance sleep. Conclusion: The study underscores DSIP-CBBBP potential in correcting neurotransmitter dysregulation and promoting sleep, hinting at its utility in sleep-related therapies.

13.
Brain Commun ; 6(5): fcae348, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39440300

RESUMO

Concussion is a public health crisis that results in a complex cascade of neurochemical changes that can have life-changing consequences. Subconcussions are generally considered less serious, but we now realize repetitive subconcussions can lead to serious neurological deficits. Subconcussions are common in contact sports and the military where certain personnel are exposed to repetitive occupational blast overpressure. Post-mortem studies show subconcussion is a better predictor than concussion for chronic traumatic encephalopathy-a progressive and fatal neurodegenerative tauopathy, only diagnosable post-mortem-thus, an in vivo biomarker would be transformative. Magnetoencephalography captures the dynamics of neuronal electrochemical action, and functional MRI shows that functional connectivity is associated with tauopathy patterns. Therefore, both imaging modalities could provide surrogate markers of tauopathy. In this cross-sectional study, we examined the effects of repetitive subconcussion on neuronal activity and functional connectivity using magnetoencephalography and functional MRI, and on neurological symptoms and mental health in a military sample. For magnetoencephalography and outcome analyses, 81 participants were split into 'high' and 'low' blast exposure groups using the generalized blast exposure value: n = 41 high blast (26.4-65.7 years; 4 females) and n = 40 low blast (28.0-63.3 years; 8 females). For functional MRI, two high blast male participants without data were excluded: n = 39 (29.6-65.7 years). Magnetoencephalography revealed disrupted neuronal activity in participants with a greater history of repetitive subconcussions, including neural slowing (higher delta activity) in right fronto-temporal lobes and subcortical regions (hippocampus, amygdala, caudate, pallidum and thalamus), and functional dysconnectivity in the posterior default mode network (lower connectivity at low and high gamma). These abnormalities were independent of concussion or traumatic stress history, and magnetoencephalography showed functional dysconnectivity not detected in functional MRI. Besides magnetoencephalography changes, those with higher blast exposure had poorer somatic and cognitive outcomes, with no blast-related differences in mental health or associations between neurological symptoms and neuronal activity. This study suggests that repetitive subconcussions have deleterious effects on brain function and that magnetoencephalography provides an avenue for both treatment targets by identifying affected brain regions and in prevention by identifying those at risk of cumulative subconcussive neurotrauma.

14.
IJID Reg ; 13: 100447, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39399128

RESUMO

Objectives: Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. This infection is more severe when combined with hepatitis Delta virus (HDV). Moreover, Plasmodium falciparum (Pf) malaria infection during pregnancy can have severe consequences for the mother and the newborn. Importantly, the manifestation of these three infections has never been described to date. Methods: Thus, we conducted a prospective study, between May 27, 2022, and April 15, 2023, and we investigated these three infections in 260 pregnant women aged 24 to 46 years, in Gabon and evaluated the impact on newborns. The sera were used to screen hepatitis B surface antigen (HBsAg) and Pf by determining HBsAg® ALERE rapid diagnostic test and malaria rapid diagnostic test kits. The positive sample was confirmed using MINI VIDAS® for HBV and Lambaréné method for "Pf". The real-time-polymerase chain reaction assay was used to amplify HBV DNA and HDV RNA on Roche instrument. Results: Our results showed that the prevalences of HBV and (Pf) infection were 4.23% (n = 11) and 34.62% (n = 90), respectively. Moreover, we found that 3.46 % (n = 9) of pregnant women infected with HBV were coinfected with HDV. The prevalence of triple infection was 1.15% (n = 3). In addition, the leukocytes and lymphocytes absolute count were significantly lower for the triple-infected pregnant women. Conclusions: We describe for the first time the triple coinfection by HBV, HDV, and Pf, which could induce a great inflammatory reaction and high liver disorder in newborns.

15.
J Biomol Struct Dyn ; : 1-19, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39403785

RESUMO

The enzyme Asparaginyl Endopeptidase (AEP) is associated with proteinopathy-related pathologies such as Alzheimer's disease (AD) and Frontal Temporal Dementia (FTD). The onset of pathologies by AEP is due to cleaved fragments forming protein aggregates resulting in neurodegeneration. Unfortunately, there are no clinically approved small molecule inhibitors for AEP, and therefore, it serves as an unmet medical need for the design and development of potential novel small molecules. In developing potential inhibitors for proteolytic activity, a structured approach utilizing structure-based computer-aided drug design (SB-CADD) parameters was employed. This involved virtual high throughput screening (vHTS) across various CNS-focused databases enriched with diverse functionality. We identified the top sixty ligands based on the glide XP-docking score out of 10 million ligands. The free binding energy was then calculated using MM-GBSA for all top selected molecules which resulted in discovering that AEPI-1 to AEPI-6 (Asparaginyl Endopeptidase inhibitors) displayed high affinity towards the catalytic triad. Further investigation determined that all top six hits form stable complexes during 50 ns molecular dynamic simulations. We also observed that AEPI-2 demonstrated the highest stability within the binding pockets. Post-MD analyses such as DCCM, PCA, PDF, and ADMET properties were also evaluated. By bridging all the observations, we observed these six molecules occupy the active site of the ß-helix (ß1, ß3, and ß4) of the S1 pocket and additional binding sites in α1 and ß5, suggesting its suitability as a potential candidate for drug discovery against Asparaginyl Endopeptidase.

16.
Mol Biol Rep ; 51(1): 1066, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39422771

RESUMO

BACK GROUND: 7-Methoxycoumarin (7-MC) is well recognized for its anti-inflammatory and anti-nociceptive actions. Its capacity to lessen neuropathic pain hasn't been documented yet. Hence the impact of 7-MC on vincristine-induced peripheral neuropathic pain in rodents was investigated. The investigation also looked at the impact of 7-MC in reducing neuropathic pain via voltage-gated calcium channels and phospholipase enzyme inhibition using pertinent in vitro and in silico methods. METHODS AND RESULTS: Vincristine (0.1 mg/kg, i.p., daily) was administered continuously for 7 days to induce peripheral neuropathic pain in mice, with cold allodynia and thermal hyperalgesia and evaluated on the 8th day using the acetone bubble test and hot water tail immersion test. In order to derive the mechanistic approach for ameliorating neuropathic pain, the role of 7-MC in the inhibition of the phospholipase enzyme, gene expression studies on voltage-gated calcium channels using mouse BV2 microglial cells and in silico studies for its calcium channel binding affinity were also performed. The test compounds reduced vincristine-induced cold allodynia and thermal hyperalgesia in mice in a dose-dependent experiments. In vitro studies on phospholipase inhibition by 7-MC showed an IC50 of 27.08 µg/ml and down-regulated the gene expression of calcium channels in the BV2 microglial cell line. In silico docking scores for 7-MCwere higher than the standard drug gabapentin. CONCLUSION: The compound 7-MC has shown promise in alleviating vincristine-induced peripheral neuropathicin mice. Studies conducted in parallel, both in silico and in vitro have demonstrated that 7-MC effectively reduces neuropathic pain. This pain reduction is achieved through two mechanisms: inhibiting the phospholipase enzyme and blocking voltage-gated calcium channels.


Assuntos
Analgésicos , Cumarínicos , Hiperalgesia , Neuralgia , Vincristina , Animais , Camundongos , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Cumarínicos/farmacologia , Vincristina/farmacologia , Hiperalgesia/tratamento farmacológico , Analgésicos/farmacologia , Masculino , Simulação por Computador , Simulação de Acoplamento Molecular , Canais de Cálcio/metabolismo , Canais de Cálcio/genética , Modelos Animais de Doenças , Linhagem Celular
17.
Biol Res Nurs ; : 10998004241288791, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39378890

RESUMO

OBJECTIVE: To explore the relationship between the high frequency (HF) heart rate variability (HRV) and electroencephalogram (EEG) delta band power in women with irritable bowel syndrome (IBS) versus healthy control women. MATERIALS AND METHODS: Twenty women with IBS and twenty healthy controls were studied over three consecutive nights using polysomnography in a sleep laboratory. To avoid the first night effect, only second-night data were analyzed. Power spectral analysis was applied to HRV and EEG recordings. The linear system coherence/phase analysis assessed the relationship between normalized HF power of HRV and normalized delta band power of EEG during the first four NREM-REM sleep cycles. RESULTS: Women with IBS exhibited a significantly higher percentage of NREM sleep, higher normalized HF, lower normalized low frequency (LF) and decreased LF/HF ratio of HRV in the first four NREM-REM sleep cycles compared to controls. Additionally, their normalized delta band power was significantly lower in these sleep cycles and over the whole night. The phase shift between HF and delta band power was significantly longer in the IBS group. While the coherence between normalized HF and normalized delta band power was lower in the IBS group, the difference was not statistically significant. CONCLUSIONS: The coherence/phase analysis showed a dysregulated interaction between autonomic and central nervous systems in women with IBS, manifested by increased lag time between cardiac and EEG delta band power compared to healthy controls. Whether this dysregulation contributes to the pathophysiology of IBS remains to be determined.

18.
Discov Oncol ; 15(1): 526, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39367924

RESUMO

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. Reviews indicated a positive relationship between exposure to pesticides and the development of cancers. In the present study, we have estimated the level of oxidative stress markers in serum samples of pesticide exposure and unexposed cancer patients as compared to normal control. We have found a significant decrease in peroxygenase (PON) and arylesterase (ARE) activity and substantial increases in homocysteine levels in both cancer groups. The level of heme biosynthesis rate-limiting enzymes delta-aminolevulinic acid dehydratase (δ-ALA-D) also significantly decreased compared to control. The statistical comparison between the cancer groups does not show significant changes. We concluded the involvement of oxidative stress in carcinogenesis in both cancer group patients. However, more study is needed to put homocysteine as a novel marker for a variety of diseases on a single platform.

19.
Histopathology ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375308

RESUMO

AIMS: Diagnosis of coeliac disease (CD) with mild mucosal changes is difficult for all parties involved. We aimed to determine the power of T cell receptor (TCR)γδ+ intra-epithelial lymphocytes (IELs) in discriminating CD from other causes of intra-epithelial lymphocytosis using a new monoclonal antibody. METHODS: A total of 167 cases categorised as coeliac (117 untreated CD, classified according to Marsh, updated by Ensari, including 29 type 1, 29 type 2, 39 type 3 and 20 treated CD), and non-coeliac groups (24 controls and 26 non-coeliac IELosis) based on clinical, serological and histological data were studied for IEL counts enumerated per 100 enterocytes using haematoxylin and eosin, CD3, TCR δ-stains. RESULTS: TCRγδ+ IELs were significantly higher in CD (24.83 ± 16.13) compared to non-CD (6.72 ± 6.32) and were correlated with the degree of mucosal damage. Both γδ+ IEL count and ratio showed higher performance in differentiating untreated coeliacs from controls, with a sensitivity of 83.76; 85.57 and specificity of 95.83; 79.17, respectively. TCRγδ+ IEL counts distinguished type 1 CD (20.41 ± 13.57) from non-coeliac IELosis (9.42 ± 7.28) (p = 0.025). Discriminant analysis revealed that villus/crypt ratio, γδ+ and CD3+ IEL counts, γδ+/CD3+IEL ratio, IEL distribution pattern were potent discriminants and correctly classified 82.3% of cases while the algorithm accurately diagnosed 93.4% of cases. CONCLUSIONS: The new antibody detecting γδ+ IELs in FFPE sections revealed thresholds of 10.5 for γδ+ IELs and 14% for γδ+/CD3+IEL ratio which distinguished coeliacs from non-coeliacs with high sensitivity and specificity, particularly in cases with normal villus/crypt axis including type 1 CD, non-CD IELosis and controls. A 'coeliac algorithm' based on γδ+ IELs is proposed with the hope that it will be used in the histopathological diagnostic approach by the pathology community.

20.
BMC Infect Dis ; 24(1): 1116, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375604

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), led to a global pandemic from 2020. In Thailand, five waves of outbreaks were recorded, with the fourth and fifth waves driven by the Delta and Omicron variants, resulting in over 20,000 new confirmed cases daily at their peaks. METHODS: This cross-sectional study investigated the associations between clinical symptoms, vaccination status, antibody responses, and post-COVID-19 sequelae in COVID-19 patients. Plasma samples and clinical data were collected from participants admitted to hospitals in Thailand between July 2021 and August 2022, with follow-ups conducted for one year. The study included 110 participants infected with either the Delta (n = 46) or Omicron (n = 64) variants. Virus genotypes were confirmed by RT-PCR of nasal swab RNA and partial nucleotide sequencing of the S gene. IgG and IgA antibody levels against the receptor-binding domain (RBD) of SARS-CoV-2 Delta and Omicron variants were measured in plasma samples using ELISA. RESULTS: Pneumonia was found to be associated with Delta variant infections, while sore throat, congestion or runny nose, and headache were linked to Omicron infections. Vaccination with fewer than two doses and diabetes mellitus were significantly associated with higher disease severity. Specific IgG and IgA antibodies against the RBD of the Delta variant generally rose by day 14 and were maintained for up to two months, whereas the pattern of antibody response to the Omicron variant was less clear. Antibody risings were found to be positively associated with pneumonia, certain underlying conditions (obesity, hypertension, dyslipidemia, and diabetes mellitus), and age ≥ 60 years. Delta variant infections were associated with forgetfulness, hair loss, and headache during the 1-year post-infection period. Females were more likely to experience hair loss, forgetfulness, and joint pain, while older age was associated with joint pain. CONCLUSIONS: This study enhances our understanding of SARS-CoV-2 infections in Thais, particularly concerning the Delta and Omicron variants. The findings can inform public health planning and response strategies for future outbreaks of SARS-CoV-2 or other emerging viral diseases.


Assuntos
Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Feminino , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Tailândia/epidemiologia , Anticorpos Antivirais/sangue , Seguimentos , Vacinação , Idoso , Imunoglobulina G/sangue , Vacinas contra COVID-19/imunologia , Imunoglobulina A/sangue , Adulto Jovem , Formação de Anticorpos
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