Active natural ingredients, especially small molecules, have recently received wide attention as modifiers used to treat neurodegenerative disease by promoting neurogenic regeneration of neural stem ...cell (NSC) in situ. 20(S)-protopanaxadiol (PPD), one of the bioactive ingredients in ginseng, possesses neuroprotective properties. However, the effect of PPD on NSC proliferation and differentiation and its mechanism of action are incompletely understood.
In this study, we investigated the impact of PPD on NSC proliferation and neuronal lineage differentiation through activation of the Wnt/glycogen synthase kinase (GSK)-3β/β-catenin pathway. NSC migration and proliferation were investigated by neurosphere assay, Cell Counting Kit-8 assay, and EdU assay. NSC differentiation was analyzed by Western blot and immunofluorescence staining. Involvement of the Wnt/GSK3β/β-catenin pathway was examined by molecular simulation and Western blot and verified using gene transfection.
PPD significantly promoted neural migration and induced a significant increase in NSC proliferation in a time- and dose-dependent manner. Furthermore, a remarkable increase in antimicrotubule-associated protein 2 expression and decrease in nestin protein expression were induced by PPD. During the differentiation process, PPD targeted and stimulated the phosphorylation of GSK-3β at Ser9 and the active forms of β-catenin, resulting in activation of the Wnt/GSK-3β/β-catenin pathway. Transfection of NSCs with a constitutively active GSK-3β mutant at S9A significantly hampered the proliferation and neural differentiation mediated by PPD.
PPD promotes NSC proliferation and neural differentiation in vitro via activation of the Wnt/GSK-3β/β-catenin pathway by targeting GSK-3β, potentially having great significance for the treatment of neurodegenerative diseases.
A new strain of coronavirus (CoV) has caused an outbreak of severe acute respiratory syndrome (SARS), with 8098 individuals being infected and 774 deaths worldwide. We carried out protein chip array ...profiling analysis in an attempt to identify biomarkers that might be useful in monitoring the clinical course of SARS patients.
We performed surface-enhanced laser desorption ionization time-of-flight mass spectrometry on 89 sera collected from 28 SARS patients, 72 sera from 51 control patients with various viral or bacterial infections, and 10 sera from apparently healthy individuals.
Nine significantly increased and three significantly decreased serum biomarkers were discovered in the SARS patients compared with the controls. Among these biomarkers, one (11,695 Da) was identified to be serum amyloid A (SAA) protein by peptide mapping and tandem mass spectrometric analysis. When we monitored the SAA concentrations longitudinally in 45 sera from four SARS patients, we found a good correlation of SAA concentration with the extent of pneumonia as assessed by a serial chest x-ray opacity score. Increased SAA occurred in three of four patients at the time of extensive pneumonia as indicated by high x-ray scores. Over the course of gradual recovery in two patients, as assessed clinically and radiologically, SAA concentrations gradually decreased. In the third patient, the concentrations were initially increased, but were further increased with superimposed multiple bacterial infections. SAA was not markedly increased in the fourth patient, who had low x-ray scores and whose clinical course was relatively mild.
Protein chip array profiling analysis could be potentially useful in monitoring the severity of disease in SARS patients.
•Protection from COVID-19 remains important, particularly for healthcare personnel.•Healthcare personnel in 22 U.S. states were enrolled in a case-control study.•Overall, a bivalent mRNA dose ...conferred 34% protection against COVID-19.•Effectiveness was similar by subgroup, but waned from 55% to 22% after two months.•Up-to-date vaccination is recommended to optimize protection against COVID-19.
Bivalent mRNA vaccines were recommended since September 2022. However, coverage with a recent vaccine dose has been limited, and there are few robust estimates of bivalent VE against symptomatic SARS-CoV-2 infection (COVID-19). We estimated VE of a bivalent mRNA vaccine dose against COVID-19 among eligible U.S. healthcare personnel who had previously received monovalent mRNA vaccine doses.
We conducted a case-control study in 22 U.S. states, and enrolled healthcare personnel with COVID-19 (case-participants) or without COVID-19 (control-participants) during September 2022–May 2023. Participants were considered eligible for a bivalent mRNA dose if they had received 2–4 monovalent (ancestral-strain) mRNA vaccine doses, and were ≥67 days after the most recent vaccine dose. We estimated VE of a bivalent mRNA dose using conditional logistic regression, accounting for matching by region and four-week calendar period. We adjusted estimates for age group, sex, race and ethnicity, educational level, underlying health conditions, community COVID-19 exposure, prior SARS-CoV-2 infection, and days since the last monovalent mRNA dose.
Among 3,647 healthcare personnel, 1,528 were included as case-participants and 2,119 as control-participants. Participants received their last monovalent mRNA dose a median of 404 days previously; 1,234 (33.8%) also received a bivalent mRNA dose a median of 93 days previously. Overall, VE of a bivalent dose was 34.1% (95% CI, 22.6%–43.9%) against COVID-19 and was similar by product, days since last monovalent dose, number of prior doses, age group, and presence of underlying health conditions. However, VE declined from 54.8% (95% CI, 40.7%–65.6%) after 7–59 days to 21.6% (95% CI 5.6%–34.9%) after ≥60 days.
Bivalent mRNA COVID-19 vaccines initially conferred approximately 55% protection against COVID-19 among U.S. healthcare personnel. However, protection waned after two months. These findings indicate moderate initial protection against symptomatic SARS-CoV-2 infection by remaining up-to-date with COVID-19 vaccines.
Non-neoplastic thyroid hyperplasia is common in terrestrial animals, secondary to nutritional imbalances or other goitrogenic compounds. Thyroid hyperplasia is relatively common in teleost fish; ...however, malignant thyroid neoplasia is rarely reported. We diagnosed cases of thyroid neoplasia in a population of jade perch (Scortum barcoo). The 3,000 affected fish had grossly apparent, bilateral pharyngeal swellings. Histologic examination confirmed proliferative thyroid lesions ranging from hyperplasia to well-differentiated follicular cell carcinoma. In addition, the younger population of animals on the farm also had bacterial septicemia and mild Dactylogyrus sp. gill infections. Feed analysis revealed a severe deficiency of iodine and vitamin C in the homemade fish diet used on the farm. The concentrations of other minerals, such as zinc, were also on the lower end of the recommended requirements for freshwater fish. The farm was using surface water in its recirculating aquaculture system. We recommended a switch to a commercial aquaculture diet, as well as to use well water rather than surface water to avoid any contaminants, and to treat the younger fish with an antibiotic for bacterial septicemia. Our case provides evidence of progression from nutritional-associated thyroid hyperplasia to neoplasia in farmed teleost fish.
The study aims to describe the characteristics and etiologic causes of intermediate uveitis (IU) patients seen by a tertiary eye center in Singapore over 8 years.
This was a retrospective analysis of ...the clinical records of consecutive new cases of IU that presented to the uveitis subspecialty clinic from 2004-2011 at Tan Tock Seng Hospital. Data collected included demographics, clinical and laboratory findings. Diagnoses were based on standardized clinical history, ophthalmological examination and investigations.
There were 66 new cases of IU, comprising 5.7% of 1168 new uveitis patients. The median age of diagnosis was 40 years (mean 39.4±15.9), with largest subgroup of the patients in the age group of 41-60 years (36.4%). The majority was Chinese (57.6%), followed by Asian Indians (18.2%) and Malays (16.7%). The ethnicity distribution was dissimilar to our ethnic distribution in Singapore (p<0.001) with an increased incidence of IU in the Asian Indian population. Most were idiopathic (59.1%) in etiology, followed by tuberculosis (TB) (15.2%). Ocular complications developed in 21 patients (31.8%), with cystoid macular edema (CME) being the commonest (28.8%). Severe vitritis occurred in 9.1% of patients, and was significantly associated with TB-associated IU (p<0.001). There was a downward trend for the incidence of the proportion of IU patients over the total uveitis patients (p = 0.021), with Spearman's rho of -0.786.
Despite the downward trend, TB-associated IU was still of higher prevalence compared to less endemic areas, emphasizing the need for increased TB surveillance. A high index of suspicion for TB-associated IU is required in patients with severe vitritis. Comparisons with other countries revealed disparities in the IU etiologies, indicating possible geographical differences. Prevalence of known immune-mediated etiologies of IU is less compared to the western population. Our study also suggests a probable predisposition of the Singapore local Indian population for IU.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: To report the epidemiology and classification of ocular inflammation at a tertiary eye care center in Singapore.
Methods: Retrospective cohort study of the clinical records of consecutive ...new cases from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database from 2004-2015.
Results: A total of 2200 patients were studied from the OASIS database. The most common anatomic diagnosis was anterior uveitis (55.9%), posterior uveitis (17.5%), panuveitis (9.6%), and intermediate uveitis (4.7%). In addition, scleritis (6.1%), keratouveitis (2.8%), retinal vasculitis (2.2%), and episcleritis (1.2%) were observed. Etiology was established in 65.1%, with 35.2% of patients associated with non-infectious etiologies. The most common etiologies found were presumed tuberculosis (7.2%), followed by cytomegalovirus infection (6.9%), herpetic infection (6.3%), HLA-B27-associated anterior uveitis (4.2%), and ankylosing spondylitis (3.8%).
Conclusions: The pattern of ocular inflammation in Singapore has similarities with both Western and Asian populations. Anterior uveitis was the most common, with non-infectious etiologies being slightly more common than infectious etiologies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Introduction
The glucagon-like peptide-1 receptor analogue (GLP-1RA) semaglutide is associated with improvements in glycaemia and cardiovascular risk factors in clinical trials. The aim of this study ...was to examine the real-world impact of semaglutide administered by injection in people with type 2 diabetes (T2D) across three secondary care sites in Wales.
Methods
A retrospective evaluation of 189 patients with T2D initiated on semaglutide between January 2019 and June 2020 with at least one follow-up visit was undertaken.
Results
At baseline, participants had a mean age of 61.1 years, mean glycated haemoglobin (HbA1c) of 77.8 mmol/mol (9.3%) and mean body weight of 101.8 kg. At 6 and 12 months of follow-up, mean HbA1c reductions of 13.3 mmol/mol (1.2%) and 16.4 mmol/mol (1.5%), respectively, were observed, and mean weight loss at 6 months was 3.0 kg (all
p
< 0.001). At 12 months, there were significant reductions in total cholesterol (0.5 mmol/L) and alanine transaminase (4.8 IU/L). Patients naïve to GLP-1RAs or with higher baseline HbA1c at baseline had greater glycaemic reductions, although clinically significant HbA1c reductions were also observed in those who switched from other GLP-1RAs, whose body mass index was < 35.0 and > 35.0 kg/m
2
or who had lower baseline HbA1c. Semaglutide was generally well tolerated, although adverse-effects limited use in 18 patients (9.5%).
Conclusion
Semaglutide provided clinically and statistically significant reductions in HbA1c, body weight, lipids and liver enzymes.
In the mammalian retina, bipolar cells and ganglion cells which stratify in sublamina a of the inner plexiform layer (IPL) show OFF responses to light stimuli while those that stratify in sublamina b ...show ON responses. This functional relationship between anatomy and physiology is a key principle of retinal organization. However, there are at least three types of retinal neurons, including intrinsically photosensitive retinal ganglion cells (ipRGCs) and dopaminergic amacrine cells, which violate this principle. These cell types have light-driven ON responses, but their dendrites mainly stratify in sublamina a of the IPL, the OFF sublayer. Recent anatomical studies suggested that certain ON cone bipolar cells make axonal or ectopic synapses as they descend through sublamina a, thus providing ON input to cells which stratify in the OFF sublayer. Using immunoelectron microscopy with 3-dimensional reconstruction, we have identified axonal synapses of ON cone bipolar cells in the rabbit retina. Ten calbindin ON cone bipolar axons made en passant ribbon synapses onto amacrine or ganglion dendrites in sublamina a of the IPL. Compared to the ribbon synapses made by bipolar terminals, these axonal ribbon synapses were characterized by a broad postsynaptic element that appeared as a monad and by the presence of multiple short synaptic ribbons. These findings confirm that certain ON cone bipolar cells can provide ON input to amacrine and ganglion cells whose dendrites stratify in the OFF sublayer via axonal synapses. The monadic synapse with multiple ribbons may be a diagnostic feature of the ON cone bipolar axonal synapse in sublamina a. The presence of multiple ribbons and a broad postsynaptic density suggest these structures may be very efficient synapses. We also identified axonal inputs to ipRGCs with the architecture described above.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: To report the pattern of posterior and panuveitis at a tertiary referral center in Singapore.
Methods: Subgroup retrospective analysis of 334 new posterior and panuveitis cases, from the ...Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database. Descriptive analysis was performed and visual outcome and complications were reported.
Results: The etiology for posterior uveitis and panuveitis was infectious in 162 patients (48.5%), non-infectious in 144 patients (43.1%), and idiopathic in 28 patients (8.4%). More patients with bilateral disease had a non-infectious etiology (n = 82, 50.9%) (p = 0.012). The most common complication was epiretinal membrane (n = 20, 12.3%) for the infectious group and cystoid macular edema (n = 12, 8.3%) for the non-infectious group.
Conclusions: The proportion of etiologies in our cohort varies from other studies. Understanding the variations and demographic associations allows the diagnosis and management of posterior and panuveitis to be further improved.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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