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1.
Transcutaneous fluorescence spectroscopy: development and characterization of a compact, portable, and fiber-optic sensor.
Sanchez, EM, Avery, J, Gan, J, Qian, J, Mandal, N, Agarwal, A, Mwiinga, M, Banda, R, Darzi, A, Kelly, P, et al
Journal of biomedical optics. 2024;(2):027003
Abstract
SIGNIFICANCE The integrity of the intestinal barrier is gaining recognition as a significant contributor to various pathophysiological conditions, including inflammatory bowel disease, celiac disease, environmental enteric dysfunction (EED), and malnutrition. EED, for example, manifests as complex structural and functional changes in the small intestine leading to increased intestinal permeability, inflammation, and reduced absorption of nutrients. Despite the importance of gut function, current techniques to assess intestinal permeability (such as endoscopic biopsies or dual sugar assays) are either highly invasive, unreliable, and/or difficult to perform in certain patient populations (e.g., infants). AIM: We present a portable, optical sensor based on transcutaneous fluorescence spectroscopy to assess gut function (in particular, intestinal permeability) in a fast and noninvasive manner. APPROACH Participants receive an oral dose of a fluorescent contrast agent, and a wearable fiber-optic probe detects the permeation of the contrast agent from the gut into the blood stream by measuring the fluorescence intensity noninvasively at the fingertip. We characterized the performance of our compact optical sensor by comparing it against an existing benchtop spectroscopic system. In addition, we report results from a human study in healthy volunteers investigating the impact of skin tone and contrast agent dose on transcutaneous fluorescence signals. RESULTS The first study with eight healthy participants showed good correlation between our compact sensor and the existing benchtop spectroscopic system [correlation coefficient (r)>0.919, p<0.001]. Further experiments in 14 healthy participants revealed an approximately linear relationship between the ingested contrast agent dose and the collected signal intensity. Finally, a parallel study on the impact of different skin tones showed no significant differences in signal levels between participants with different skin tones (p>0.05). CONCLUSIONS In this paper, we demonstrate the potential of our compact transcutaneous fluorescence sensor for noninvasive monitoring of intestinal health.
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2.
Degradation and dechlorination of trichloroacetic acid induced by an in situ 222 nm KrCl* excimer radiation.
Gan, J, Zhu, T, Zhang, Y, Li, D, Li, T, Zhao, M, Zhao, Z, Wang, L
Chemosphere. 2023;:138753
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Abstract
Since the coronavirus disease 2019 (COVID-19) pandemic epidemic, the excessive usage of chlorinated disinfectants raised the substantial risks of disinfection by-products (DBPs) exposure. While several technologies may remove the typical carcinogenic DBPs, trichloroacetic acid (TCAA), their application for continuous treatment is limited due to their complexity and expensive or hazardous inputs. In this study, degradation and dechlorination of TCAA induced by an in situ 222 nm KrCl* excimer radiation as well as role of oxygen in the reaction pathway were investigated. Quantum chemical calculation methods were used to help predict the reaction mechanism. Experimental results showed that UV irradiance increased with increasing input power and decreased when the input power exceeded 60 W. Decomposition and dechlorination were simultaneously achieved, where around 78% of TCAA (0.62 mM) can be eliminated and 78% dechlorination within 200 min. Dissolved oxygen showed little effect on the TCAA degradation but greatly boosted the dechlorination as it can additionally generate hydroxyl radical (•OH) in the reaction process. Computational results showed that under 222 nm irradiation, TCAA was excited from S0 to S1 state and then decayed by internal crossing process to T1 state, and a reaction without potential energy barrier followed, resulting in the breaking of C-Cl bond and finally returning to S0 state. Subsequent C-Cl bond cleavage occurred by a barrierless •OH insertion and HCl elimination (27.9 kcal/mol). Finally, the •OH attacked (14.6 kcal/mol) the intermediate byproducts, leading to complete dechlorination and decomposition. The KrCl* excimer radiation has obvious advantages in terms of energy efficiency compared to other competitive methods. These results provide insight into the mechanisms of TCAA dechlorination and decomposition under KrCl* excimer radiation, as well as important information for guiding research toward direct and indirect photolysis of halogenated DBPs.
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Metabolomic study combined with the low-level light therapy of Chinese acupuncture points and combined oral contraceptives in treatment of primary dysmenorrhea: A prospective, multicenter, randomized controlled study.
Wang, H, Zhu, S, Ding, X, Deng, Y, Ma, X, Gan, J, Wang, Y, Sun, A
Heliyon. 2023;(3):e13821
Abstract
OBJECTIVE To compare the changes of metabolites between Low-level light therapy (LLLT) and combined oral contraceptive (COC) after treatment of primary dysmenorrhea (PD), and to compare and analyze the biological and biochemical effects of the two treatments by analyzing the differences in metabolite profiles. METHODS A multicenter, double-blind, prospective, parallel, randomized controlled study was conducted on 69 women aged 16-35 years old with PD who were randomly divided into COC treatment group or LLLT treatment group. Low-level light therapy with light-emitting diodes (LED) was applied on two acupoints named "Guanyuan" (CV4) and "Qihai" (CV6). After 12 weeks of treatment intervention, blood samples were collected before and after treatment for metabolomic analysis. We used UPLC-MS/MS analysis to compare the differences in metabolite changes between LLLT and COC before and after treatment. RESULTS 76 differential metabolites were detected in the LLLT group, and 92 differential metabolites were detected in the COC group, which were up-regulated or down-regulated (p < 0.001). Prostaglandin D2 (PG D2) was down-regulated and biliverdin was up-regulated after LLLT treatment, 4a-Hydroxytetrahydrobiopterin, Prostaglandin D2, 5-Hydroxy-l-tryptophan, Cholic acid were down-regulated and cortisol was up-regulated after COC treatment, and the differences were statistically significant. Cortisol and testosterone glucuronide in LLLT group were significantly lower than those in COC group. The metabolic pathways affected were glycerophospholipid metabolism, linoleic acid metabolism and arachidonic acid metabolism in the LLLT group, and glycerophospholipid metabolism, folate biosynthesis, arachidonic-acid-metabolism, and tryptophan metabolism in the COC group. The differential metabolic pathway were linoleic acid metabolism, steroid hormone biosynthesis, and alpha-Linolenic acid metabolism after the comparison of LLLT with COC. CONCLUSION LLLT and COC might relieve dysmenorrhea by down-regulating PGD2, and LLLT might also relieve dysmenorrhea by up-regulating biliverdin. The level of cortisol and testosterone glucuronide after LLLT treatment was lower than that after COC treatment, which might lead to the difference in the clinical efficacy of the two treatments for dysmenorrhea.
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The Mechanisms of the Potential Probiotic Lactiplantibacillus plantarum against Cardiovascular Disease and the Recent Developments in its Fermented Foods.
Wang, Z, Wu, J, Tian, Z, Si, Y, Chen, H, Gan, J
Foods (Basel, Switzerland). 2022;(17)
Abstract
Cardiovascular disease (CVD) has become the leading cause of death worldwide. Many recent studies have pointed out that Lactiplantibacillus plantarum (Lb. plantarum) has great potential in reducing the risk of CVD. Lb. plantarum is a kind of lactic acid bacteria (LAB) widely distributed in fermented food and the human intestinal tract, some strains of which have important effects on human health and the potential to be developed into probiotics. In this review, we summarize the mechanism of potential probiotic strains of Lb. plantarum against CVD. It could regulate the body's metabolism at the molecular, cellular, and population levels, thereby lowering blood glucose and blood lipids, regulating blood pressure, and ultimately reducing the incidence of CVD. Furthermore, since Lb. plantarum is widely utilized in food industry, we highlight some of the most important new developments in fermented food for combating CVD; providing an insight into these fermented foods can assist scientists in improving the quality of these foods as well as alleviating patients' CVD symptoms. We hope that in the future functional foods fermented by Lb. plantarum can be developed and incorporated into the daily diet to assist medication in alleviating CVD to some extent, and maintaining good health.
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Pyridoxine-responsive KCNQ2 epileptic encephalopathy: Additional cases and literature review.
Chen, J, Tao, Q, Fan, L, Shen, Y, Liu, J, Luo, H, Yang, Z, Liang, M, Gan, J
Molecular genetics & genomic medicine. 2022;(10):e2024
Abstract
BACKGROUND Typical patients with KCNQ2 (OMIM# 602235) epileptic encephalopathy present early neonatal-onset intractable seizures with a burst suppression EEG pattern and severe developmental delay or regression, and those patients always fail first-line treatment with sodium channel blockers. Vitamin B6, either pyridoxine or pyridoxal 50-phosphate, has been demonstrated to improve seizure control in intractable epilepsy. METHODS Here, we collected and summarized the clinical data for four independent cases diagnosed with pyridoxine-responsive epileptic encephalopathy, and their exome sequencing data. Moreover, we reviewed all published cases and summarized the clinical features, genetic variants, and treatment of pyridoxine-responsive KCNQ2 epileptic encephalopathy. RESULTS All four cases showed refractory seizures during the neonatal period or infancy, accompanied by global development delay. Four pathogenetic variants of KCNQ2 were uncovered and confirmed by Sanger sequencing: KCNQ2 [NM_172107.4: c.2312C > T (p.Thr771Ile), c.873G > C (p.Arg291Ser), c.652 T > A (p.Trp218Arg) and c.913-915del (p. Phe305del)]. Sodium channel blockers and other anti-seizure medications failed to control their seizures. The frequency of seizures gradually decreased after treatment with high-dose pyridoxine. In case 1, case 2, and case 4, clinical seizures relapsed when pyridoxine was withdrawn, and seizures were controlled again when pyridoxine treatment was resumed. CONCLUSION Our study suggests that pyridoxine may be a promising adjunctive treatment option for patients with KCNQ2 epileptic encephalopathy.
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A splicing variation in NPRL2 causing familial focal epilepsy with variable foci: additional cases and literature review.
Zhang, J, Shen, Y, Yang, Z, Yang, F, Li, Y, Yu, B, Chen, W, Gan, J
Journal of human genetics. 2022;(2):79-85
Abstract
NPRL2 (nitrogen permease regulator like 2) is a component of the GATOR1(GAP activity towards rags complex 1) proteins, which is an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). However, FFEVF caused by NPRL2 variants has not been widely explored. Here, we describe a variant, 339+2T>C, in NPRL2 identified by trio whole-exome sequencing (WES) in a family. This splicing variant that occurred at the 5' end of exon 3 was confirmed by minigene assays, which affected alternative splicing and led to exon 3 skipping in NPRL2. Our cases presented multiple seizure types (febrile seizures, infantile spasms, focal seizures, or focal to generalized tonic-clonic seizures). Electroencephalogram (EEG) showed frequent discharges in the left frontal and central regions. A favorable prognosis was achieved in response to vitamin B6 and topiramate when the patient was seven months old. Our study expands the phenotype and genotype spectrum of FFEVF and provides solid diagnostic evidence for FFEVF.
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Contaminants of emerging concerns in recycled water: Fate and risks in agroecosystems.
Shi, Q, Xiong, Y, Kaur, P, Sy, ND, Gan, J
The Science of the total environment. 2022;:152527
Abstract
Recycled water (RW) has been increasingly recognized as a valuable source of water for alleviating the global water crisis. When RW is used for agricultural irrigation, many contaminants of emerging concern (CECs) are introduced into the agroecosystem. The ubiquity of CECs in field soil, combined with the toxic, carcinogenic, or endocrine-disrupting nature of some CECs, raises significant concerns over their potential risks to the environment and human health. Understanding such risks and delineating the fate processes of CECs in the water-soil-plant continuum contributes to the safe reuse of RW in agriculture. This review summarizes recent findings and provides an overview of CECs in the water-soil-plant continuum, including their occurrence in RW and irrigated soil, fate processes in agricultural soil, offsite transport including runoff and leaching, and plant uptake, metabolism, and accumulation. The potential ecological and human health risks of CECs are also discussed. Studies to date have shown limited accumulation of CECs in irrigated soils and plants, which may be attributed to multiple attenuation processes in the rhizosphere and plant, suggesting minimal health risks from RW-fed food crops. However, our collective understanding of CECs is rather limited and knowledge of their offsite movement and plant accumulation is particularly scarce for field conditions. Given a large number of CECs and their occurrence at trace levels, it is urgent to develop strategies to prioritize CECs so that future research efforts are focused on CECs with elevated risks for offsite contamination or plant accumulation. Irrigating specific crops such as feed crops and fruit trees may be a viable option to further minimize potential plant accumulation under field conditions. To promote the beneficial reuse of RW in agriculture, it is essential to understand the human health and ecological risks imposed by CEC mixtures and metabolites.
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8.
Geriatric nutritional risk index as a predictor of complications and long-term outcomes in patients with gastrointestinal malignancy: a systematic review and meta-analysis.
Xie, H, Tang, S, Wei, L, Gan, J
Cancer cell international. 2020;(1):530
Abstract
BACKGROUND The effect of the geriatric nutritional risk index (GNRI) on the prognosis of patients with gastrointestinal malignancy remains unclear. The aim of our study was to systematically explore the value of the GNRI in evaluating postoperative complications and long-term outcomes in gastrointestinal malignancy. METHODS A systematic literature search was conducted using electronic databases to report the impact of the GNRI on postoperative complications and long-term outcomes of patients with gastrointestinal malignancies as of August 2020. The hazard ratio (HR) with a 95% confidence interval (CI) was used to evaluate the impact of the GNRI on long-term outcomes. The risk ratio (RR) with 95% CI was used to assess the impact of the GNRI on postoperative complications. RESULT A total of nine studies with 2,153 patients were enrolled in our meta-analysis. The results suggested that a low GNRI was correlated with poor overall survival of patients with gastrointestinal malignancy (HR = 1.94, 95% CI 1.65-2.28, p < 0.001). Patients with a low GNRI had a higher risk of complications than patients with a high GNRI (OR = 2.19, 95% CI 1.57-3.05, p < 0.001). In addition, patients with a low GNRI had shorter relapse-free survival (HR = 2.45, 95% CI 1.50-4.00, p < 0.001) and disease-free survival (HR = 1.84, 95% CI 1.23-2.76, p = 0.003) than those with a high GNRI. However, the GNRI was not an independent factor affecting cancer-specific survival (HR = 1.60, 95% CI 0.91-2.82, p = 0.101). CONCLUSION Based on existing evidence, the GNRI was a valuable predictor of complications and long-term outcomes in patients with gastrointestinal malignancy.
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COVID-19 infection: the perspectives on immune responses.
Shi, Y, Wang, Y, Shao, C, Huang, J, Gan, J, Huang, X, Bucci, E, Piacentini, M, Ippolito, G, Melino, G
Cell death and differentiation. 2020;27(5):1451-1454
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Plain language summary
The SARS-CoV-2 infection triggers an immune response which varies greatly from one person to another. It can be roughly divided into three stages: stage I, an asymptomatic incubation period with or without detectable virus; stage II, non-severe symptomatic period with the presence of virus; stage III, severe respiratory symptomatic stage with high viral load. Currently around 15% of people infected end up in severe stage III. There appears to be a two-phase immune response; an early protective phase and a second inflammation-driven damaging phase. In phase one the adaptive immune system responds to the virus. Being in good general health is important in this phase to limiting the progression of the disease to a more severe stage. In phase two the innate immune system response to tissue damage caused by the virus could lead to widespread inflammation of the lungs and acute respiratory distress syndrome or respiratory failure. Therapeutically this raises the question of whether the immune response should be boosted in phase one and suppressed in phase two. There also appears to be an element of viral relapse in some patients discharged from hospital indicating that a virus-eliminating immune response may be difficult to achieve naturally. These same patients may also not respond to vaccines. Overall, it is still unclear why some people develop severe disease, whilst others do not. Overall immunity alone does not explain the differences in disease presentation.
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Evidence for the Validity of Pyridoxic Acid (PDA) as a Plasma-Based Endogenous Probe for OAT1 and OAT3 Function in Healthy Subjects.
Shen, H, Holenarsipur, VK, Mariappan, TT, Drexler, DM, Cantone, JL, Rajanna, P, Singh Gautam, S, Zhang, Y, Gan, J, Shipkova, PA, et al
The Journal of pharmacology and experimental therapeutics. 2019;(1):136-145
Abstract
Plasma pyridoxic acid (PDA) and homovanillic acid (HVA) were recently identified as novel endogenous biomarkers of organic anion transporter (OAT) 1/3 function in monkeys. Consequently, this clinical study assessed the dynamic changes and utility of plasma PDA and HVA as an initial evaluation of OAT1/3 inhibition in early-phase drug development. The study was designed as a single-dose randomized, three-phase, crossover study; 14 Indian healthy volunteers received probenecid (PROB) (1000 mg orally) alone, furosemide (FSM) (40 mg orally) alone, or FSM 1 hour after receiving PROB (40 and 1000 mg orally) on days 1, 8, and 15, respectively. PDA and HVA plasma concentrations remained stable over time in the prestudy and FSM groups. Administration of PROB significantly increased the area under the plasma concentration-time curve (AUC) of PDA by 3.1-fold (dosed alone; P < 0.05), and 3.2-fold (coadministered with FSM; P < 0.01), compared with the prestudy and FSM groups, respectively. The corresponding increase in HVA AUC was 1.8-fold (P > 0.05) and 2.1-fold (P < 0.05), respectively. The increases in PDA AUC are similar to those in FSM AUC, whereas those of HVA are smaller (3.1-3.2 and 1.8-2.1 vs. 3.3, respectively). PDA and HVA renal clearance (CL R) values were decreased by PROB to smaller extents compared with FSM (0.35-0.37 and 0.67-0.73 vs. 0.23, respectively). These data demonstrate that plasma PDA is a promising endogenous biomarker for OAT1/3 function and that its plasma exposure responds in a similar fashion to FSM upon OAT1/3 inhibition by PROB. The magnitude and variability of response in PDA AUC and CL R values between subjects is more favorable relative to HVA.