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1.
Cell Mol Life Sci ; 81(1): 86, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38349432

RESUMEN

Glucose-stimulated insulin secretion (GSIS) in pancreatic islet ß-cells primarily relies on electrophysiological processes. Previous research highlighted the regulatory role of KCNH6, a member of the Kv channel family, in governing GSIS through its influence on ß-cell electrophysiology. In this study, we unveil a novel facet of KCNH6's function concerning insulin granule exocytosis, independent of its conventional electrical role. Young mice with ß-cell-specific KCNH6 knockout (ßKO) exhibited impaired glucose tolerance and reduced insulin secretion, a phenomenon not explained by electrophysiological processes alone. Consistently, islets from KCNH6-ßKO mice exhibited reduced insulin secretion, conversely, the overexpression of KCNH6 in murine pancreatic islets significantly enhanced insulin release. Moreover, insulin granules lacking KCNH6 demonstrated compromised docking capabilities and a reduced fusion response upon glucose stimulation. Crucially, our investigation unveiled a significant interaction between KCNH6 and the SNARE protein regulator, Munc18-1, a key mediator of insulin granule exocytosis. These findings underscore the critical role of KCNH6 in the regulation of insulin secretion through its interaction with Munc18-1, providing a promising and novel avenue for enhancing our understanding of the Kv channel in diabetes mechanisms.


Asunto(s)
Exocitosis , Insulina , Animales , Ratones , Fenómenos Electrofisiológicos , Glucosa , Secreción de Insulina
2.
Reprod Biol Endocrinol ; 20(1): 45, 2022 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-35255928

RESUMEN

Diabetes mellitus (DM), a high incidence metabolic disease, is related to the impairment of male spermatogenic function. Spermidine (SPM), one of the biogenic amines, was identified from human seminal plasma and believed to have multiple pharmacological functions. However, there exists little evidence that reported SPM's effects on moderating diabetic male spermatogenic function. Thus, the objective of this study was to investigate the SPM's protective effects on testicular spermatogenic function in streptozotocin (STZ)-induced type 1 diabetic mice. Therefore, 40 mature male C57BL/6 J mice were divided into four main groups: the control group (n = 10), the diabetic group (n = 10), the 2.5 mg/kg SPM-treated diabetic group (n = 10) and the 5 mg/kg SPM-treated diabetic group (n = 10), which was given intraperitoneally for 8 weeks. The type 1 diabetic mice model was established by a single intraperitoneal injection of STZ 120 mg/kg. The results showed that, compare to the control group, the body and testis weight, as well the number of sperm were decreased, while the rate of sperm malformation was significantly increased in STZ-induced diabetic mice. Then the testicular morphology was observed, which showed that seminiferous tubule of testis were arranged in mess, the area and diameter of which was decreased, along with downregulated anti-apoptotic factor (Bcl-2) expression, and upregulated pro-apoptotic factor (Bax) expression in the testes. Furthermore, testicular genetic expression levels of Sertoli cells (SCs) markers (WT1, GATA4 and Vimentin) detected that the pathological changes aggravated observably, such as the severity of tubule degeneration increased. Compared to the saline-treated DM mice, SPM treatment markedly improved testicular function, with an increment in the body and testis weight as well as sperm count. Pro-apoptotic factor (Bax) was down-regulated expression with the up-regulated expression of Bcl-2 and suppression of apoptosis in the testes. What's more, expression of WT1, GATA4, Vimentin and the expressions of glycolytic rate-limiting enzyme genes (HK2, PKM2, LDHA) in diabetic testes were also upregulated by SPM supplement. The evidence derived from this study indicated that the SMP's positive effect on moderating spermatogenic disorder in T1DM mice's testis. This positive effect is delivered via promoting spermatogenic cell proliferation and participating in the glycolytic pathway's activation.


Asunto(s)
Diabetes Mellitus Experimental , Glucólisis/efectos de los fármacos , Infertilidad Masculina , Espermatogénesis/efectos de los fármacos , Espermidina/farmacología , Animales , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Infertilidad Masculina/tratamiento farmacológico , Infertilidad Masculina/etiología , Infertilidad Masculina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Análisis de Semen , Espermatogénesis/fisiología , Espermidina/uso terapéutico , Estreptozocina , Testículo/efectos de los fármacos , Testículo/metabolismo
3.
J Org Chem ; 87(5): 3799-3803, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35020395

RESUMEN

The C-S activation and sulfur removal from native thiols is challenging, which limits their application as feedstock materials in organic synthesis despite their natural abundance. Herein, we introduce a per-/polyfluoroaryl moiety, which serves as a redox-active scaffold, into sp3-hybridized thiols to activate the C-S bond. Using a Ni catalyst with MgBr2 as an additive, the S group can be removed to yield an aliphatic radical that can react with an aryl halide in a reductive cross-coupling.


Asunto(s)
Compuestos de Sulfhidrilo , Azufre , Catálisis , Estructura Molecular , Oxidación-Reducción , Compuestos de Sulfhidrilo/química
4.
J Geriatr Psychiatry Neurol ; 33(6): 363-369, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-31830849

RESUMEN

OBJECTIVE: Sleep-wake disturbances, such as excessive daytime somnolence (EDS), are nonmotor symptoms of Parkinson's disease (PD) and significantly affect the quality of life. This study aimed to examine the relationship between EDS and motor and nonmotor symptoms of PD. METHODS: Eighty-two patients with idiopathic mild PD were followed up twice a year for 2 years and assessed on sleep, mood, anxiety, cognition, function, and disease severity. Data were analyzed retrospectively, comparing motor and nonmotor outcomes between those with EDS and those without. RESULTS: At baseline, 27.9% had EDS and were similar in demographic and clinical characteristics to those without; 10% had persistent EDS during the first year of follow-up. Excessive daytime somnolence had a significant main effect on mood and anxiety as shown by consistently higher scores on the Geriatric Depression Scale (P = .022) and Hospital Anxiety and Depression Scale-Anxiety subscale scores (P = .011) throughout duration of follow-up. The group with persistent EDS showed greater rate of worsening Frontal Assessment Battery scores by the end of first-year follow-up (P = .025) and greater rate of worsening Apathy Scale scores by the end of 2-year follow-up (P = .002). No significant effects of EDS on motor symptoms and disease severity were found. CONCLUSIONS: In a Southeast Asian cohort of patients with PD, EDS had a negative longitudinal impact on mood, anxiety, apathy, and cognitive function but no impact on motor symptoms and disease severity. Excessive daytime somnolence is thus a potential therapeutic target to improve nonmotor outcomes.


Asunto(s)
Trastornos de Somnolencia Excesiva/epidemiología , Trastornos de Somnolencia Excesiva/etiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Calidad de Vida/psicología , Afecto , Anciano , Ansiedad/fisiopatología , Ansiedad/psicología , Apatía , Pueblo Asiatico , Cognición/fisiología , Estudios de Cohortes , Depresión/fisiopatología , Depresión/psicología , Trastornos de Somnolencia Excesiva/etnología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/etnología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Sueño/fisiología
5.
Bioprocess Biosyst Eng ; 43(12): 2243-2252, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32671549

RESUMEN

Heterotrophic or mixotrophic culture of microalgae is feasible alternative approach to avoid light limitation in autotrophic culture. However, only a few kinds of organic carbon sources are available for algal culture. Disaccharides, such as sucrose, are difficult to be utilized by microalgae under both heterotrophic and mixotrophic conditions. In this study, a symbiotic yeast was accidentally found in a contaminated algal suspension. The symbiotic yeast was isolated and identified as Cryptococcus sp. This yeast was able to extracellularly hydrolyze sucrose and accumulated monosaccharides in the medium. It can enhance algal growth using sucrose as the carbon source at both heterotrophic and mixotrophic modes when mix-cultured with Chlorella pyrenoidosa. The highest algal cell density of 118.8 × 106 and 151.2 × 106 cells/mL was achieved with a final algal percentage of 83.5 and 93.2% at heterotrophic and mixotrophic culture, respectively. Furthermore, the protein and lipid content was significantly enhanced by mix-culture C. pyrenoidosa with Cryptococcus YZU-1. The fatty acid accumulated in this co-culture system was suitable for the production of biodiesel. This symbiotic yeast solved the problem that C. pyrenoidosa cannot heterotrophically or mixotrophically utilize sucrose. A high algae density was obtained and the protein and lipid accumulation were also significantly enhanced. This study provided a novel approach for production of protein or lipid-rich biomass using sucrose or sucrose-rich wastes as the carbon source.


Asunto(s)
Carbono/metabolismo , Chlorella/crecimiento & desarrollo , Saccharomyces cerevisiae/metabolismo , Sacarosa/metabolismo , Procesos Autotróficos , Biocombustibles , Biomasa , Carbohidratos/química , Chlorella/microbiología , Técnicas de Cocultivo , Disacáridos , Ácidos Grasos/metabolismo , Procesos Heterotróficos , Microbiología Industrial , Lípidos/biosíntesis , Lípidos/química , Microalgas/crecimiento & desarrollo , Microalgas/metabolismo , Monosacáridos/metabolismo , Filogenia , Sacarosa/química , Temperatura
6.
Pharm Biol ; 58(1): 636-645, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32634340

RESUMEN

CONTEXT: Fructus Meliae toosendan extracts (FMTE) have a good therapeutic effect on coccidiosis, but there is no relevant research on its prophylactic effect on coccidiosis. OBJECTIVE: This study comprehensively evaluates the anticoccidial effect of FMTE. MATERIALS AND METHODS: In vitro, the unsporulated oocysts were treated with serial dilutions of FMTE and incubated for 7 d, and the sporulated oocysts were counted for calculating the median lethal concentration (LC50) of FMTE. In vivo, 180 10-day-old broiler chickens free of coccidiosis were weighted and randomly distributed into six groups: normal group, untreated group, 4 protective groups (positive group and three FMTE groups). From day 10 to day 21, chickens in the three FMTE groups were pre-treated with FMTE at the dosage of 2.5, 5 and 10 g/kg/d, respectively, and chickens in the positive group were pre-treated with qiuliling (10 g/kg/d). On day 14, chickens in all groups except the normal group were orally infected with 1.5 × 104 sporulated oocysts. The clinical symptoms were observed from day 10 to day 21, the anticoccidial index (ACI), tissue lesions, and intestinal microflora were determined on day 21. RESULTS: FMTE showed anti-sporulation effect against E. tenella and the LC50 value was 245.83 µg/mL in vitro. In vivo, FMTE at the dosage of 10 g/kg/d was effective against E. tenella infection, and its ACI value was 162.56, which was higher than the value of positive drug qiuliling (128.81). Discussion and conclusions: FMTE have potent anticoccidial effects, and it presents an alternative anticoccidial agent for avian coccidiosis control.


Asunto(s)
Coccidiosis/prevención & control , Meliaceae/química , Extractos Vegetales/farmacología , Enfermedades de las Aves de Corral/prevención & control , Animales , Pollos , Coccidiosis/veterinaria , Coccidiostáticos/administración & dosificación , Coccidiostáticos/aislamiento & purificación , Coccidiostáticos/farmacología , Relación Dosis-Respuesta a Droga , Eimeria tenella/efectos de los fármacos , Frutas , Dosificación Letal Mediana , Oocistos/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Enfermedades de las Aves de Corral/parasitología
7.
Opt Express ; 27(19): 27046-27061, 2019 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-31674573

RESUMEN

We present an efficient and faithful hyperentanglement purification protocol (hyper-EPP) for three-photon system in mixed hyperentangled Greenberger-Horne-Zeilinger states with bit-flip errors in both spatial-mode and polarization degrees of freedom (DOFs), resorting to the fidelity-robust quantum gates and hyperentanglement link. Our high-efficiency hyper-EPP comes from two aspects. One is to pump the higher-fidelity hyperentanglement from different three-photon systems into the same three-photon system with fidelity-robust swap gates, the other is to reproduce some hyperentangled three-photon systems from hyperentangled two-photon subsystems based on hyperentanglement link. Moreover, as the infidelity originating from imperfect single-photon scattering can be heralded as a failure by triggering a detector, our hyper-EPP operates faithfully with the present quantum circuits. Furthermore, our hyper-EPP can be directly extended to purify multiple photon systems entangled in one DOF or hyperentangled in multiple DOFs.

8.
J Neurol Neurosurg Psychiatry ; 90(6): 681-687, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30683708

RESUMEN

BACKGROUND: Global hippocampal atrophy is a hallmark of Alzheimer's dementia and has been similarly reported in Parkinson's disease dementia (PDD). However, there is limited literature on the differential involvement of hippocampal subfields in predicting conversion to PDD. This study is an extension of previous findings on progression to mild cognitive impairment in Parkinson's disease (PD). METHODS: This cohort study recruited 73 non-demented participants with idiopathic PD (age 65.80±8.17, 75.3% male) from an outpatient neurology clinic. All participants underwent clinical assessment, neuropsychological testing and 3T MRI scans at baseline and 18 months while on prescribed dopaminergic medication. Hippocampal subfield volumes were obtained using automatic segmentation in FreeSurfer V.6.0. Participants who progressed to PDD and those who did not were compared on hippocampal subfield atrophy and cognitive change (episodic memory, attention, executive functions, language, visuospatial abilities). Subfields were further examined for their abilities to predict PDD conversion and distinguish PDD from non-demented PD using receiver operating characteristic analysis. RESULTS: Smaller baseline global hippocampal volume, cornu ammonis (CA) subfield CA1, subiculum and presubiculum volumes were observed in participants who went on to develop dementia, and predicted PDD conversion. Those who progressed to PDD saw greater decline in global hippocampal volume, granule cell layer of the dentate gyrus, presubiculum, parasubiculum and fimbria. Decline in subiculum and fimbria volume corresponded to cognitive decline in attention and executive functions, respectively. CONCLUSIONS: Early atrophy of CA1, subiculum and presubiculum preceded, and predicted, PDD conversion. Differential patterns of subfield atrophy were also observed among those who progressed to PDD and were associated with impaired executive functions.


Asunto(s)
Región CA1 Hipocampal/patología , Demencia/patología , Enfermedad de Parkinson/patología , Anciano , Antiparkinsonianos/uso terapéutico , Atrofia , Región CA1 Hipocampal/diagnóstico por imagen , Demencia/diagnóstico por imagen , Demencia/etiología , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/tratamiento farmacológico
9.
Sheng Li Xue Bao ; 71(5): 732-740, 2019 Oct 25.
Artículo en Zh | MEDLINE | ID: mdl-31646327

RESUMEN

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by loss of dopaminergic (DA) neurons in the dense part of the substantia nigra (SNpc). Postmortem analysis of PD patients and experimental animal studies found that microglial cell activation and increased levels of pro-inflammatory factors were common features of PD brain tissue. At the same time, the invasion and accumulation of peripheric immune cells were detected in the brain of PD patients. In this paper, peripheral inflammation across the blood-brain barrier (BBB), the misfolded α-synuclein (α-syn)-induced microglial cell activation and intracerebral inflammation in PD are summarized, providing potential therapeutic measures for delaying the onset of PD.


Asunto(s)
Inflamación/patología , Enfermedad de Parkinson/patología , Sustancia Negra/patología , Animales , Barrera Hematoencefálica , Neuronas Dopaminérgicas/patología , Humanos , Microglía , alfa-Sinucleína
10.
Anal Chem ; 90(5): 3196-3204, 2018 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-29430921

RESUMEN

With the continuous exposure of environmental pollutants in organisms, determination of abundance variation and spatial distribution of lipids might expand our understanding of toxicological mechanisms occurring in the kidney. Herein, an integrated method involving mass spectrometry (MS)-based lipidomics and matrix-assisted laser desorption/ionization-MS imaging (MALDI-MSI) was developed for the study of nephrotoxicity in mice exposed to 10 and 100 µg bisphenol S (BPS)/kg body weight/day. The BPS exposure remarkable perturbed abundances of 91 potential markers that mainly involved in five metabolic pathways. We elucidated the lipids spatial heterogeneity by using morphological analysis, probabilistic latent semantic analysis, and coregistered multimodal three-dimensional (3D)-MSI. In morphological analysis, both 10 and 100 µg BPS induced significant nephrotoxicity to mice, including glomerular necrosis in renal cortex, cloudy swelling in renal medulla, and interstitial collapsing in renal pelvis. Significant differential signaling lipids such as sphingomyelin (SM) (d22:0/20:4), ceramide (Cer) (d18:2/24:1), and sphingosine (d18:0) related to inflammation were found to be up-regulated and colocalized in the renal cortex, medulla, and pelvis, respectively. Also, seven significant differential lipids, which are considered to be involved in membrane homeostasis and cellular function, were found to be colocalized in the renal cortex. The observed significant variations of morphology, lipid accumulation, and metabolism in the renal cortex implicated that lipids in the renal cortex were more sensitive to BPS exposure than those in the renal medulla and pelvis. Moreover, we reconstructed a 3D-MSI model of kidney and identified two heterogeneous-related substructures in the renal cortex and pelvis upon 100 µg BPS exposure. It might be used in novel specificity evaluation and early diagnosis for environmental pollutant-induced kidney diseases.


Asunto(s)
Enfermedades Renales/metabolismo , Lípidos de la Membrana/metabolismo , Metabolómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Animales , Femenino , Humanos , Enfermedades Renales/inducido químicamente , Ratones Endogámicos BALB C , Fenoles , Sulfonas , Distribución Tisular
11.
Clin Rehabil ; 32(12): 1666-1675, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30037276

RESUMEN

OBJECTIVE:: To evaluate the effectiveness of acupuncture for pain relief and function improvement in patients with knee osteoarthritis and to determine the feasibility of an eight-week acupuncture intervention. DESIGN:: Pilot randomized controlled trial. SETTING:: Three teaching hospitals in China. SUBJECTS:: Patients with knee osteoarthritis (Kellgren grade II or III). INTERVENTIONS:: Patients were randomly assigned to an eight-week (three sessions per week) intervention of either traditional Chinese acupuncture or sham acupuncture. MAIN MEASURES:: The primary outcome was response rate-the proportion of patients achieving score ⩾36% decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function at week 8 compared with baseline. Secondary outcomes included pain, function and quality of life. RESULTS:: Of 42 patients randomized, 36 (85.7%) completed the study. There was no significant difference in response rate between the traditional Chinese acupuncture and control groups: 61.9% (13 of 21) versus 42.9% (9 of 21) achieved score ⩾36% decrease in WOMAC pain and function at week 8 ( P = 0.217). The sum of WOMAC pain and function scores at week 8 was 11.6 (9.1) in the traditional Chinese acupuncture group compared with 16.3 (10.9) in the control group ( P = 0.183). There was no significant difference between groups. Three adverse events were recorded and were classified as mild. CONCLUSION:: It showed that three sessions per week acupuncture intervention of knee osteoarthritis was feasible and safe. No difference was observed between groups due to small sample size. Larger (sample size ⩾ 296) randomized controlled trials of this intervention appear justified.


Asunto(s)
Terapia por Acupuntura , Osteoartritis de la Rodilla/terapia , Anciano , China , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Recuperación de la Función , Método Simple Ciego , Resultado del Tratamiento
12.
J Pediatr Surg ; 59(2): 254-257, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37968149

RESUMEN

INTRODUCTION: This study aims to find out the optimal timing for herniotomy for premature infants with inguinal hernia (IH): early during hospitalisation or delayed after hospital discharge. METHOD: A retrospective cohort study was conducted on premature infants diagnosed with IH during their initial hospitalization between 2015 and 2020. Demographic data and clinical outcomes were compared between infants undergoing herniotomy before discharge ("early") and those who were discharged without herniotomy ("delayed"). Student's t-test or Mann-Whitney U test and Fisher's exact test were used for statistical analysis. RESULTS: Of 219 premature infants, 189 (86.3%) underwent early herniotomy, while 30 were discharged with unoperated IH. In the delayed group, 15 (50%) underwent planned delayed herniotomy, and the remaining 15 experienced spontaneous resolution (absence of inguinal bulge over at least 1-year follow-up). The gestational age and birth weight of both groups were similar. At surgery, the delayed group median (interquartile range) was significantly older (42.1[38-49] vs 37.7 [36-40] weeks, p < 0.001) and heavier (3.27 [2.21-4.60] vs 2.22 [2.00-2.70] kg, p < 0.001). Two infants (1%) in the early group presented with incarcerated IH requiring urgent operation. In the delayed group, no infant developed incarcerated IH while awaiting elective operation (time from diagnosis to operation 44 [21-85] days). There was no statistically significant difference in respiratory and surgical complications between the two groups, although the delayed group had lesser surgical complications (0% vs 9.5%). CONCLUSION: Deferring herniotomy after discharge for premature infants is safe with close monitoring and associated with a chance of spontaneous resolution. LEVEL OF EVIDENCE: Level III, treatment study.


Asunto(s)
Hernia Inguinal , Enfermedades del Prematuro , Humanos , Recién Nacido , Hernia Inguinal/cirugía , Herniorrafia , Hospitales , Recien Nacido Prematuro , Enfermedades del Prematuro/epidemiología , Enfermedades del Prematuro/cirugía , Alta del Paciente , Estudios Retrospectivos , Lactante
13.
World J Nucl Med ; 23(2): 147-150, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38933073

RESUMEN

Phyllodes tumor is a rare fibroepithelial neoplasm of the breast. This tumor tends to spread by hematogenous route, with common metastatic sites in the lungs, bones, and liver. Metastases to the pleura, stomach, pancreas, kidneys, and adrenal gland are rare. We present a case of a 52-year-old lady with malignant phyllodes tumor of breast undergone local tumor resection, followed by solitary lung metastasis with lobectomy, and subsequently diagnosed of multiple new metastatic sites in pleura, stomach, pancreas, kidneys, adrenal gland, and bone detected on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography within 2 years.

14.
PNAS Nexus ; 3(6): pgae214, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38881838

RESUMEN

The digital health field is experiencing substantial growth due to its potential for sustained and longitudinal deployment. In turn, this may drive improved monitoring and intervention as catalysts for behavioral change compared to traditional point-of-care practices. In particular, the increase in incidence of population health challenges such as diabetes, heart disease, fatty liver disease, and other disorders coupled with rising healthcare costs have emphasized the importance of exploring technical, economics, and implementation considerations, among others in the decentralization of health and healthcare innovations. Both healthy individuals and patients stand to benefit from continued technical advances and studies in these domains. To address these points, this study reports a N-of-1 study comprised of sustained regimens of intermittent fasting, fitness (strength and cardiovascular training), and high protein, low carbohydrate diet and parallel monitoring. These regimens were paired with serial blood ketone, blood glucose (wearable and finger stick) and blood pressure readings, as well as body weight measurements using a collection of devices. Collectively this suite of platforms and approaches were used to monitor metabolic switching from glucose to ketones as energy sources-a process associated with potential cardio- and neuroprotective functions. In addition to longitudinal biomarker dynamics, this work discusses user perspectives on the potential role of harnessing digital devices to these dynamics as potential gamification factors, as well as considerations for the role of biomarker monitoring in health regimen development, user stratification, and potentially informing downstream population-scale studies to address metabolic disease, healthy aging and longevity, among other indications.

15.
Nucl Med Commun ; 45(8): 710-717, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38726624

RESUMEN

OBJECTIVES: The study aimed to evaluate the frequency of incidental suspicious lesions detected by flourine-18 fluorodeoxyglucose PET/computed tomography ( 18 F-FDG PET/CT) scans done for staging or restaging in adult cancer patients. We further determined the detection rate of synchronous and metachronous malignancies in these suspicious lesions after further investigations. MATERIALS AND METHODS: This retrospective analysis evaluated the consecutive patients with 18 F-FDG PET/CT scans done in Queen Elizabeth Hospital (QEH), Hong Kong between July 2021 and June 2022. The adult cancer patients who underwent staging or restaging 8 F-FDG PET/CT were included while the remaining were excluded. Patients' demographics, primary cancer type, tumor markers, and pathological analyses for the incidental suspicious lesions were reviewed to establish the detection rate of synchronous and metachronous malignancies. RESULTS: A total of 2054 patients fulfilled inclusion criteria with age ranging from 18 to 93 years old. Out of the 2054 patients, 304 (14.8%) were found to have incidental suspicious lesions. Of these, 206 patients (67.8%) underwent further investigations including pathological analyses. Subsequently, 84 of these 206 patients (40.8%) had pathologically proven synchronous or metachronous malignancies. CONCLUSION: The detection rate of incidental suspicious lesions in adult cancer patients who underwent 18 F-FDG PET/CT scans for staging or restaging was 14.8% and the rate of synchronous and metachronous malignancies in these suspicious lesions was 40.8%. The treatment plan of these patients may potentially be altered, which should be included in the cost-benefit analysis of using this imaging modality.


Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias Primarias Secundarias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Masculino , Femenino , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Primarias Secundarias/diagnóstico por imagen , Adulto Joven , Adolescente , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias/diagnóstico por imagen
16.
Chem Asian J ; 19(3): e202301004, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38102804

RESUMEN

Dihydroquinazolinone (DHQZ) has recently been harnessed as a ketone-derived pro-aromatic reagent extensively employed in (metalla)photoredox reactions as versatile group transfer agents. In this work, we outline a column chromatography-free protocol for the multigram-scale synthesis of pro-aromatic DHQZs as well as its use in a gram-scale nickel/photoredox dual-catalyzed cross-coupling in single-batch, photoflow, and simultaneous multiple smaller batches. While the single-batch approach leveraged moderate yields, a simple plug-flow photoreactor also exhibited amenable productivity (up to 45 % yield) despite the use of a heterogeneous base. Meanwhile, performing the metallaphotoredox-catalyzed reaction in multiple smaller batches in an improvised photoreactor facilitated high yields of up to 59 % and good reproducibility, implying a convenient alternative in the absence of photoflow setups.

17.
NPJ Regen Med ; 9(1): 13, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38519518

RESUMEN

Neural progenitor cells (NPCs) derived from human pluripotent stem cells(hPSCs) provide major cell sources for repairing damaged neural circuitry and enabling axonal regeneration after spinal cord injury (SCI). However, the injury niche and inadequate intrinsic factors in the adult spinal cord restrict the therapeutic potential of transplanted NPCs. The Sonic Hedgehog protein (Shh) has crucial roles in neurodevelopment by promoting the formation of motorneurons and oligodendrocytes as well as its recently described neuroprotective features in response to the injury, indicating its essential role in neural homeostasis and tissue repair. In this study, we demonstrate that elevated SHH signaling in hNPCs by inhibiting its negative regulator, SUFU, enhanced cell survival and promoted robust neuronal differentiation with extensive axonal outgrowth, counteracting the harmful effects of the injured niche. Importantly, SUFU inhibition in NPCs exert non-cell autonomous effects on promoting survival and neurogenesis of endogenous cells and modulating the microenvironment by reducing suppressive barriers around lesion sites. The combined beneficial effects of SUFU inhibition in hNPCs resulted in the effective reconstruction of neuronal connectivity with the host and corticospinal regeneration, significantly improving neurobehavioral recovery in recipient animals. These results demonstrate that SUFU inhibition confers hNPCs with potent therapeutic potential to overcome extrinsic and intrinsic barriers in transplantation treatments for SCI.

18.
Biomolecules ; 14(3)2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38540790

RESUMEN

Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various organisms, remains unexplored in diatoms. This study reveals the vital role of Spd, synthesized through the spermidine synthase (SDS)-based pathway, in the growth of the diatom Phaeodactylum tricornutum. PtSDS1 and PtSDS2 in the P. tricornutum genome were confirmed as SDS enzymes through enzyme-substrate selectivity assays. Their distinct activities are governed primarily by the Y79 active site. Overexpression of a singular gene revealed that PtSDS1, PtSDS2, and PtSAMDC from the SDS-based synthesis pathway are all situated in the cytoplasm, with no significant impact on PA content or diatom growth. Co-overexpression of PtSDS1 and PtSAMDC proved essential for elevating Spd levels, indicating multifactorial regulation. Elevated Spd content promotes diatom growth, providing a foundation for exploring PA functions and regulation in diatoms.


Asunto(s)
Diatomeas , Diatomeas/genética , Diatomeas/metabolismo , Espermidina Sintasa/genética , Espermidina Sintasa/metabolismo , Poliaminas/metabolismo , Vías Biosintéticas , Genoma
20.
BJR Case Rep ; 9(2): 20220144, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36998334

RESUMEN

Interpretation of FDG PET images in oncology patients is in general a visual exercise of search for focal increased uptake (hypermetabolism). However, in some cases, hypometabolism (focal decreased uptake) can matter as much as hypermetabolism. We report three cases of FDG PET studies for oncological indications. All of them showed focal hypometabolic lesions suspicious of metastases. The diagnoses were then supported either by histological proof and/or follow-up imaging studies. The importance of being alert to both focal hypermetabolism and focal hypometabolism when interpreting FDG PET images is underscored.

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