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Temporal metabolic trajectory analyzed by LC-MS/MS based targeted metabolomics in acute pancreatitis pathogenesis and Chaiqin Chengqi decoction therapy

Phytomedicine. 2022 Feb 17;99:153996. doi: 10.1016/j.phymed.2022.153996. Online ahead of print.

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of pancreas that lacks effective specific drugs as well as gold standard laboratory tests for diagnosis and severity assessment. Chaiqin chengqi decoction (CQCQD) has been proven to alleviate the severity and mortality of AP, but its underlying mechanisms remain incompletely understood.

PURPOSE: To investigate the correlation between metabolic trajectories of the serum and pancreas, the metabolic pathways with respect to the onset and progression of AP, and investigate the effect of CQCQD in modulating the dysregulated pancreatic metabolism of AP.

METHODS: Serum and pancreas samples from cerulein-induced AP mice were collected for pathology, biochemical index assessment, LC-MS/MS based metabolomics and functional validation over the course of 1 – 24 h. The temporal trends of pancreatic and serum metabolites in AP were analyzed using Mfuzz clustering algorithm, and their associations were revealed by Pearson correlation analysis. The metabolic trajectories and pathways across multi-timepoints were analyzed by univariate and multivariate statistical analyses, and the AP-related metabolic pathways were further screened by metabolite correlation and network interaction analyses. Finally, the changes in metabolite levels and metabolic trajectory after CQCQD therapy were identified, and the altered expression of related metabolic enzymes was verified by RT-qPCR, western blotting, and immunohistochemistry.

RESULTS: Amino acid metabolism was significantly altered in the pancreas and serum of AP, but with different trends. The unsynchronized “open” and “closed” metabolic trajectories in pancreas and serumrevealed that metabolic processes occur earlier in peripheral rather than local tissue, with the most obvious changes occuring at 12 h in the pancreas which were also consistent with the inflammation score results. Several amino acid intermediates showed strong positive correlation between serum and pancreas, and therein serum cystathionine was positively correlated to 33 pancreatic metabolites. In particular, the correlations between the levels of pancreatic cystathionine and methionine, serine, and glutathione (GSH) emphasized the importance of trans-sulfuration to GSH metabolism for AP progression. CQCQD treatment reversed the metabolic trajectory of the pancreas, and also restored the levels of cystathionine and glutathione synthase.

CONCLUSION: Our results have defined a unique time-course metabolic trajectory for AP progression in both the serum and pancreas; it has also revealed a key role of CQCQD in reversing AP-associated metabolic alterations, thus providing new metabolic targets for the treatment and prognosis of AP.

PMID:35231826 | DOI:10.1016/j.phymed.2022.153996

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MiRNA-155 inhibition enhances porcine embryo preimplantation developmental competence by upregulating ZEB2 and downregulating ATF4

Theriogenology. 2022 Feb 22;183:90-97. doi: 10.1016/j.theriogenology.2022.02.019. Online ahead of print.

ABSTRACT

The in vitro embryo’s competence is lower than in vivo counterparts and miRNAs found to affect the developmental competence, affecting pluripotency, stress level and apoptosis in embryos. We aimed to investigate the effect of miRNA-155 on parthenogenically activated early development porcine embryos at the preimplantation blastocyst stage. We designed miRNA-155 mimics and inhibitors and microinjected them into post-activated oocytes. The embryonic cleavage rate, blastocyst rate, and embryo development quality in terms of stress and apoptosis levels were investigated by confocal microscopy. Furthermore, we selected target genes, analyzed gene interaction and prediction networks, and compared the gene expression level in treatments and controls. miRNA-155 inhibition improved in vitro developmental competence by increasing cell numbers and reducing stress and apoptosis levels. The cleavage rate in the miRNA-155 inhibitor group was significantly higher (P < 0.05) than that in the miRNA-155 mimic group, but not in the control, whereas the blastocyst rate of the miRNA-155 inhibitor group was statistically significantly higher (P < 0.05) than in both control and miRNA-155 mimic groups. The relative gene expression level analysis showed downregulation of mRNAs related to stress and apoptosis, BAX, and the stress-induced autophagy gene ATF4, and TNF-ɑ in the miRNA-155 inhibitor group. Moreover, miRNA-155 inhibition showed upregulation of the relative expression of OCT4, ZEB2, BCL2, and IL-1 mRNA compared to control and mimic groups. However, the miRNA-155 mimic-injected group showed lower cleavage rates and blastocyst development rates than the other two groups. In conclusion, miRNA-155 inhibition in porcine in vitro embryos improved their preimplantation developmental competence and in vitro embryo production.

PMID:35231827 | DOI:10.1016/j.theriogenology.2022.02.019

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An integrated strategy for anti-inflammatory quality markers screening of traditional Chinese herbal medicine Mume Fructus based on phytochemical analysis and anti-colitis activity

Phytomedicine. 2022 Feb 20;99:154002. doi: 10.1016/j.phymed.2022.154002. Online ahead of print.

ABSTRACT

BACKGROUND: Mume Fructus (MF) is used in traditional Chinese herbal medicine (TCM) to treat chronic cough, prolonged diarrhea, and other inflammation-related diseases. It is processed from Prunus mume fruit (PM) by drying at low temperature according to the Chinese Pharmacopoeia. The standard quality control method includes measurement of citric acid content, which is not sufficient to determine its clinical efficacy. In addition, the quality markers, that would ensure consistent drug composition and stability during extraction and processing of the drug, are currently not available.

PURPOSE: This study sought to determine and analyze the bioactive compounds in MF and to establish the quality maker evaluation system, which would enable accurate assessment of different processing and extraction approaches for MF preparation.

STUDY DESIGN AND METHODS: First, a UPLC-QTOF-MS/MS method was established to identify the chemical constituents of PM and MF. Second, the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-treated rats were used to assess anti-inflammatory activity of water and ethanol extracts of PM and MF. Third, correlation analysis and multivariate statistical analysis was used to seek the candidate quality markers of MF. Fourth, molecular docking was used to predict the potential mechanism of identified compounds for the anti-inflammatory activity. Finally, a UPLC method was established to quantify the selected quality markers in MF products, that were prepared by different drying processes.

RESULTS: 99 components (28 newly reported) were identified from PM and MF. During the drying process several changes in the composition were observed; caffeoylquinic acids were degraded to p-coumaric acid, caffeic acid, protocatechuic acid, or p-hydroxybenzoic acid; multi-acetyl p-coumaroyl sucroses were degraded to mumeose R and p-coumaroyl-3-O-sucrose. On the other hand, contents of mumefural and amygdalin increased after drying process. In colitis rats, MF reduced more NO levels to greater extent in comparison to PM, which could be attributed to the presence of caffeic acid, p-coumaric acid, protocatechuic acid, p-hydroxybenzoic acid, mumefural, p-coumaroyl-3-O-sucrose, mumeose R, and amygdalin in MF. Moreover, water extracts were better than ethanol extracts in alleviating the IL-1β, IL-6, and IL-17 levels, possibly on account of citric acid and caffeoylquinic acids. The predicted mechanism of action could be through inhibition of the production of NLRP3, TLR4, and NF-κB proteins. Finally, 7 compounds (citric acid, 3-O-caffeoylquinic acid, 5-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, caffeic acid, protocatechuic acid, and p-coumaric acid) were selected as quality markers of MF that could be used for the process quality control.

CONCLUSION: This study revealed the material basis of PM and MF for anti-colitis activity and discovered the quality markers of MF which could reflect the anti-inflammatory activity and the processing process of MF.

PMID:35231824 | DOI:10.1016/j.phymed.2022.154002

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Enriched autoinducer-2 (AI-2)-based quorum quenching consortium in a ceramic anaerobic membrane bioreactor (AnMBR) for biofouling retardation

Water Res. 2022 Feb 17;214:118203. doi: 10.1016/j.watres.2022.118203. Online ahead of print.

ABSTRACT

This study is the first to enrich a facultative QQ consortium for AI-2-based quorum sensing (QS) disruption (FQQ2) and discover its quorum quenching (QQ) performance in an anaerobic membrane bioreactor (AnMBR) for membrane fouling retardation. Herein, FQQ2 was enriched by the enrichment culture using 4,5-dihydroxy-2,3-pentanedione (DPD) followed by anaerobic screening. FQQ2 was composed of various facultative AI-2-based QQ microorganisms including Acinetobacter, Comamonas, Stenotrophomonas, and FQQ2 was capable to degrade 96.96% of DPD in 9 h. More importantly, FQQ2 prolonged membrane filtration operation by an average of 3.72 times via reduction of DPD in the AnMBR treating domestic wastewater (p ≤ 0.05). QQ was implicated to reduce the content of proteins and carbohydrates of the extracellular polymeric substances (EPS) of suspended biomass by 24.16% and 10.39%, respectively, and concentration of proteins of the soluble microbial products (SMP) by 18.77%. Parallel factor (PARAFAC) modelling of excitation-emission matrix (EEM) demonstrated that QQ could reduce the content of fulvic acid-like and humic acid-like substances, aromatic proteins and soluble-microbial-by-product-like proteins of the EPS (p ≤ 0.05) and abate the content of soluble-microbial-by-product-like proteins in the SMP (p ≤ 0.05). The lower EPS content of suspended biomass could be rendered with the reduced relative abundance of AI-2-regulated Christensenellaceae;g-, Hyphomicrobium, Leucobacter and Microbacterium by 48.48%, 76.56%, 64.78% and 59.26%, respectively, and QQ led to the reduction of the relative abundance of Christensenellaceae;g- and Leucobacter in the cake layer by 31.07% and 51.43%, respectively. Moreover, quantity of organics as well as planktonic microorganisms in the supernatant decreased in presence of FQQ2 (p ≤ 0.05). Of note, markedly lower relative abundance of AI-2-regulated Sulfurovum in supernatant by 97.74% resulted in its lower abundance of cake layer. Intriguingly, in the presence of QQ, methane production was statistically enhanced by 62.5% (p ≤ 0.05). It was closely linked to the decrease of sulfate reduction (p ≤ 0.05), which resulted from 37.93% lower abundance of sulfate-reduction Desulfomonile in the suspended biomass (p ≤ 0.05). Collectively, this study sheds lights on the development of AI-2-based QQ for biofouling control in AnMBRs.

PMID:35231804 | DOI:10.1016/j.watres.2022.118203

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The burden of multiple sclerosis among postpartum women and self management’s challenges: Pilot study of supportive program

Mult Scler Relat Disord. 2022 Feb 23;60:103694. doi: 10.1016/j.msard.2022.103694. Online ahead of print.

ABSTRACT

BACKGROUND: This study aims to determine the effect of multiple sclerosis supportive programs on mothers’ self-management during postpartum.

STUDY DESIGN: A quasi-experimental, nonequivalent group design was utilized. Primigravida pregnant women between 35-37 weeks of gestation and recently diagnosed with multiple sclerosis participated in two preparation sessions. While the first session during pregnancy was an open conversation about the delivery, the key topics of the second session were the nature of the postpartum cycle and the expected relapses.

RESULTS: Seventy pregnant women with multiple sclerosis participated in this research. Results denoted a statistical difference between both groups regarding self-management in 6th and 12th weeks postpartum. The improvements were related to mothers’ relationships with their health care providers and knowledge and information about multiple sclerosis during this transitional phase. On the other hand, there were no differences among both groups related to their levels of functional activities at 6th and 12th weeks postpartum. Although there was a slight deterioration in motor ability score among both groups at 12th week’s postpartum, 54.3% of the intervention group vs. 49% of the non-intervention group reported 100% absolute independence. Moreover, the total relapses in the three-month postpartum ranged between 1-6, increasing the frequency of relapses during the three-month postpartum with no statistically significant differences between both groups.

CONCLUSION: Conducting a multidisciplinary program to follow and counsel mothers with MS helps enhance self-management throughout the three-month postpartum period.

PMID:35231803 | DOI:10.1016/j.msard.2022.103694

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Characteristics of suicide attempts associated with lethality and method: A latent class analysis of the Military Suicide Research Consortium

J Psychiatr Res. 2022 Feb 21;149:54-61. doi: 10.1016/j.jpsychires.2022.02.016. Online ahead of print.

ABSTRACT

While suicide prevention is a national priority, particularly among service members and veterans (SMVs), understanding of suicide-related outcomes remains poor. Person-centered approaches (e.g., latent class analysis) have promise to identify unique risk profiles and subgroups in the larger population. The current study identified latent subgroups characterized by prior self-directed violence history and proximal risk factors for suicide among suicide attempt survivors, and compared subgroups on demographics and most-lethal attempt characteristics. Participants included civilians and SMVs reporting lifetime suicide attempt(s) (n = 2643) from the Military Suicide Research Consortium. Two classes emerged from Common Data Elements: suicide attempt and non-suicidal self-injury frequency, suicide attempt method, perceived likelihood of future suicide, suicide disclosure, suicide intent, and perceived and actual lethality of attempt. A Higher-Risk History class was characterized by greater intent to die, certainty about attempt fatality and method lethality, belief injury would be medically unfixable, and likelihood of prior non-suicidal self-injury. A Lower-Risk History class was characterized by greater ambivalence toward death and methods. Higher-Risk class members were more likely to be male, older, SMVs, have less formal education, use firearms as most-lethal attempt method, and require a higher degree of medical attention. Lower-Risk class members were more likely to be female, civilian, use cutting as most-lethal attempt method, and require less medical attention for attempts. Findings have implications for risk assessments and highlight the importance of subjective perceptions about suicidal behavior. Further investigation of real-time individual-level is necessary, especially for SMVs who may be at greatest risk for potentially lethal suicidal behavior.

PMID:35231792 | DOI:10.1016/j.jpsychires.2022.02.016

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Abundance and characteristics of microplastics in gastrointestinal tracts and gills of croaker fish (Johnius dussumieri) from off Mumbai coastal waters of India

Mar Pollut Bull. 2022 Feb 26;176:113473. doi: 10.1016/j.marpolbul.2022.113473. Online ahead of print.

ABSTRACT

The present study was conducted to establish the intensity of microplastic pollution in demersal fish species, Johnius dussumieri, from the north eastern coastal waters of the Arabian sea. MP recovered were analysed for size, morphology, colour, and polymer type. The study results indicated that the GI tract and gills of individual fishes had 6.6 ± 1.7 and 6.2 ± 1.7 items, respectively. The microplastics having a size of <100 μm consisting of beads were found to be most predominant. Black and blue were the most present colours of microplastic in the tissues. Among the different studied months, a higher number of MP incidence was observed in the post monsoon period. There is no significant correlation observed between the microplastic numbers in gills and guts tissue. The present study shows that there is a potential risk of microplastic bioaccumulation in the fish body and subsequent risk to the consumers and organisms sharing the food chain.

PMID:35231784 | DOI:10.1016/j.marpolbul.2022.113473

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Early modulation of Angiopoietin-2 plasma levels predicts benefit from regorafenib in patients with metastatic colorectal cancer

Eur J Cancer. 2022 Feb 26;165:116-124. doi: 10.1016/j.ejca.2022.01.025. Online ahead of print.

ABSTRACT

BACKGROUND: No biomarkers are currently available to predict the efficacy of trifluridine/tipiracil (FTD/TPI) in chemorefractory metastatic colorectal cancer. The multicohort REGOLAND study aims at exploring and validating circulating markers potentially able to predict benefit from regorafenib in this setting.

MATERIAL AND METHODS: In the retrospective ‘regorafenib exploratory cohort’, including 105 patients treated with regorafenib, baseline (d1) plasma levels of angiogenesis-related biomarkers and their early modulation after 15 days (d15) of treatment were investigated for correlation with clinical outcome. Based on a pre-specified statistical hypothesis, main retrospective findings were prospectively challenged in the ‘regorafenib validation cohort’, including 100 patients treated with regorafenib. Prospectively validated putative biomarkers were then assessed in the control ‘FTD/TPI cohort’, including 93 patients treated with FTD/TPI.

RESULTS: In the ‘regorafenib exploratory cohort’, the early (d15) increase of Angiopoietin-2 (Ang-2) was associated with longer progression-free survival (HR:0.57 [95%CI:0.38-0.88], P = 0.004) and a trend towards longer OS (HR:0.74 [95%CI:0.48-1.14], P = 0.165), than the early decrease. Similar results were prospectively confirmed in the ‘regorafenib validation cohort’ (HR for progression-free survival:0.72 [95%CI:0.48-1.08], P = 0.095; HR for OS:0.77 [95%CI:0.51-1.16], P = 0.204). No predictive impact was shown for the early modulation of Ang-2 in the ‘FTD/TPI cohort’. High baseline Ang-2 levels predict poor prognosis in all the investigated cohorts, independently of other clinical prognostic variables.

CONCLUSIONS: The early modulation of circulating Ang-2 predicts the efficacy of regorafenib. Baseline Ang-2 plasma levels are an independent prognostic biomarker in chemorefractory metastatic colorectal cancer.

PMID:35231767 | DOI:10.1016/j.ejca.2022.01.025

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A systematic review and meta-analysis of early childhood intervention programs for developmental difficulties in low-and-middle-income countries

Asian J Psychiatr. 2022 Feb 15;70:103026. doi: 10.1016/j.ajp.2022.103026. Online ahead of print.

ABSTRACT

Early acknowledgment of developmental difficulties in young children strengthens both preventive and therapeutic approaches. Despite their feasibility, early intervention services are limited in Low-and-Middle-Income (LAMI) countries compared to high income countries. The aim of this study was to examine the evidence for early childhood intervention programs for developmental difficulties in children below five years in LAMI countries through a systematic review and meta-analysis. In this background, original studies published in peer-reviewed journals from 2010 to 2019 with a focus on developmental difficulties including delays and deviances; randomized research design with a clear description of the intervention and measurable outcomes, and conducted in LAMI countries were considered for the systematic review. Electronic databases, including ProQuest, PubMed, Ovid, EBSCOhost, and Google Scholar, were searched using a combination of specific keywords. PRISMA guidelines were followed to include the studies. Each of the selected study was assessed for quality before applying appropriate statistics to synthesize the data. Fourteen publications were identified from 2697 publications for the systematic review, out of which four were found compatible for a meta-analysis. The studies reviewed were conducted in Bangladesh, India, Pakistan, Uganda, Vietnam, and Zambia. A meta-analysis of four studies provided considerable evidence for the effects of early developmental intervention. This systematic review provides an evidence for early childhood intervention programs in LAMI countries. Implications of these findings for the early childhood programs are discussed in this article.

PMID:35231776 | DOI:10.1016/j.ajp.2022.103026

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Environmental detection of Mycoplasma hyopneumoniae in breed-to-wean farms

Res Vet Sci. 2022 Feb 5;145:188-192. doi: 10.1016/j.rvsc.2022.02.009. Online ahead of print.

ABSTRACT

There is a need to develop cost-effective and non-invasive approaches to sample large populations to evaluate the disease status of breeding herds. In this study we assessed the detection of the M. hyopneumoniae genetic material in environmental surfaces and air of farrowing rooms, and skin (udder, snout and vagina) of lactating sows at weaning, in farms having different M. hyopneumoniae infection status (negative, positive sub-clinically infected and positive clinically affected). Mycoplasma hyopneumoniae was detected in air, air deposition particles, dam and stall surfaces of the positive clinically affected herd. Mycoplasma hyopneumoniae could only be detected in dam and stall surfaces in sub-clinically infected herds. Mycoplasma hyopneumoniae was not detected in all samples collected in the negative herd. The cycle threshold of the positive PCR samples were not statistically different between sample types or farms. However, a significant difference (p < 0.05) was observed in the percentage of positive samples between the positive clinically affected farm and the rest. Likewise, M. hyopneumoniae was detected in the environment and surfaces at weaning in positive breeding herds. Further testing and validation is recommended for environmental and surface samples before they can be employed as part of the M. hyopneumoniae diagnostic process. In addition, results from this study highlight potential sources of M. hyopneumoniae infection for piglets in breeding herds, especially during an outbreak.

PMID:35231720 | DOI:10.1016/j.rvsc.2022.02.009