Kaempferol-3-O-(2″-O-galloyl-ß-D-glucopyranoside): a novel neuroprotective agent from Diospryros kaki against cerebral ischemia-induced brain injury.

Our previous study demonstrated neuroprotective and therapeutic effects of a standardized flavonoid extract from leaves of Diospyros kaki L.f. (DK) on middle cerebral artery occlusion-and-reperfusion (MCAO/R)-induced brain injury and its underlying mechanisms. This study aimed to clarify flavonoid components responsible for the effects of DK using in vitro and in vivo transient brain ischemic models. Organotypic hippocampal slice cultures (OHSCs) subjected to oxygen- and glucose-deprivation (OGD) were performed to evaluate in vitro neuroprotective activity of DK extract and nine isolated flavonoid components. MCAO/R mice were employed to elucidate in vivo neuroprotective effects of the flavonoid component that exhibited the most potent neuroprotective effect in OHSCs. DK extract and seven flavonoids [quercetin, isoquercetin, hyperoside, quercetin-3-O-(2″-O-galloyl-ß-D-galactopyranoside), kaempferol, astragalin, and kaempferol-3-O-(2″-O-galloyl-ß-D-glucopyranoside) compound (9)] attenuated OGD-induced neuronal cell damage and compound (9) possessed the most potent neuroprotective activity in OHSCs. The MCAO/R mice showed cerebral infarction, massive weight loss, characteristic neurological symptoms, and deterioration of neuronal cells in the brain. Compound (9) and a reference drugs, edaravone, significantly attenuated these physical and neurological impairments. Compound (9) mitigated the blood-brain barrier dysfunction and the change of glutathione and malondialdehyde content in the MCAO mouse brain. Edaravone suppressed the oxidative stress but did not significantly affect the blood-brain barrier permeability. The present results indicated that compound (9) is a flavonoid constituent of DK with a potent neuroprotective activity against transient ischemia-induced brain damage and this action, at least in part, via preservation of blood-brain barrier integrity and suppression of oxidative stress caused by ischemic insult.

Rare T263P epidermal growth factor receptor extracellular domain mutation of advanced non-small cell lung cancer in a Vietnamese male patient.

T263P mutation is one of the rare EGFR mutations located on chromosome 7p11.2, which is a change in amino acid residue at position 263 of the epidermal growth factor receptor protein, where L-threonine has been replaced by L-proline. This missense mutation in the extracellular EGFR domain is not well-known in lung cancer. In this study, we first report a patient with advanced lung adenocarcinoma harbouring only a rare T263P EGFR mutation who benefited from first-line afatinib therapy in Vietnam. The patient achieved a partial response with a time-to-treatment failure of 5 months. The patient subsequently received several chemotherapy regimens as the disease progressed, with overall survival of 17 months. Non-small cell lung cancer with a rare T263P EGFR mutation responds to afatinib but has a poor prognosis. Further studies are needed to determine the efficacy of targeted therapies in this specific population.

PD-L1-negative non-small cell lung cancer harbouring a rare BRAF mutation with successful treatment of first-line pembrolizumab plus chemotherapy: A case report and review the literature.

BRAF mutations are uncommon in non-small cell lung cancer (NSCLC), accounting for less than 5% of all NSCLC cases. The utilization of targeted therapies in non-V600E BRAF mutant NSCLC is considered controversial, although non-V600E genotype is reported in ~50% of all BRAF mutant patients. We document the case of a 63-year-old patient with NSCLC harbouring a rare BRAF E501Q mutation, who had prolonged response to immunotherapy combined with chemotherapy in Vietnam. The patient was diagnosed with metastatic PD-L1-negative lung adenocarcinoma and received pembrolizumab plus chemotherapy as first-line treatment. After completing 35 cycles of pembrolizumab and pemetrexed, his disease has remained stable during the treatment-free follow-up period, and he is alive 38 months after treatment initiation at the latest follow-up. Immune-based therapy is an appropriate option for lung adenocarcinoma with rare non-V600E BRAF mutation. Further clinical studies are necessary to determine the effectiveness of using immune-based therapy in this specific population.

Anti-hypertensive effects of Callisia fragrans extract on Reno-vascular hypertensive rats.

OBJECTIVES: This study aims to investigate the anti-hypertensive effects of aqueous extract of Callisia fragrans and their underlying mechanism using a two-kidney one-clip (2K1C) model of reno-vascular hypertension in rats. METHODS: The reno-vascular hypertensive rats were treated with C. fragrans leaf extract (100 and 500 mg/kg; p.o.) and a reference drug, captopril (20 mg/kg; p.o.), for 4 weeks. The blood pressure and heart rate were recorded using a tail-cuff. The heart weight, left ventricular wall thickness, and serum creatinine and urea levels were measured. A spectrophotometric assay was used to analyze the angiotensin-converting enzyme (ACE) inhibition activity of the extract and the reference drug. The total volume and the concentration of sodium, potassium, and chloride in urine samples were evaluated. RESULTS: C. fragrans extract significantly reduced both systolic and diastolic blood pressures in the reno-vascular hypertensive rats. No significant difference in the heart rate was observed between each animal group. C. fragrans extract reduced the 2K1C-induced increase in the heart and body weight ratio and the left ventricular wall thickness. Moreover, the extract also attenuated the increase in serum urea induced by the 2K1C treatment. C. fragrans extract inhibited ACE activity in vitro with an IC50 of 20.97 ± 3.94 µg/ml. The urine output and urinary electrolyte excretion significantly increased in C. fragrans extract-treated rats. CONCLUSIONS: These findings demonstrated that C. fragrans extract can mitigate hypertension and alleviate ventricular hypertrophy and renal dysfunction in reno-vascular hypertensive rats, at least in part via ACE activity inhibition and diuretic property.

Ocimum sanctum Linn. Extract Improves Cognitive Deficits in Olfactory Bulbectomized Mice via the Enhancement of Central Cholinergic Systems and VEGF Expression.

This study aimed to clarify the antidementia effects of ethanolic extract of Ocimum sanctum Linn. (OS) and its underlying mechanisms using olfactory bulbectomized (OBX) mice. OBX mice were treated daily with OS or a reference drug, donepezil (DNP). Spatial and nonspatial working memory performance was measured using a modified Y maze test and a novel object recognition test, respectively. Brain tissues of the animals were subjected to histochemical and neurochemical analysis. OS treatment attenuated OBX-induced impairment of spatial and nonspatial working memories. OBX induced degeneration of septal cholinergic neurons, enlargement of the lateral ventricles, and suppression of hippocampal neurogenesis. OS and DNP treatment also depressed these histological damages. OS administration reduced ex vivo activity of acetylcholinesterase in the brain. OBX diminished the expression levels of genes coding vascular endothelial growth factor (VEGF) and VEGF receptor type 2 (VEGFR2). Treatment with OS and DNP reversed OBX-induced decrease in VEGF gene and protein expression levels without affecting the expression of the VEGFR2 gene. These results demonstrate that the administration of OS can lessen the cognitive deficits and neurohistological damages of OBX and that these actions are, at least in part, mediated by the enhancement of central cholinergic systems and VEGF expression.

Pathological Complete Response with Neoadjuvant Trastuzumab Combined with Chemotherapy in HER2 Positive Breast Cancer: A Single Institution Retrospective Analysis from Vietnam.

PURPOSE: Neoadjuvant regimens containing trastuzumab and chemotherapy were widely used in human epidermal growth factor 2 (HER2) positive breast cancer patients. In this article, we report complete pathological response (pCR) rates from a single institution in Vietnam. PATIENTS AND METHODS: Medical records of HER2 positive breast cancer patients who received neoadjuvant treatment with trastuzumab combined with chemotherapy were reviewed. Information on patient demographics, breast cancer stage, pathology reports, surgical data, and treatment regimens were collected. Pathological response was evaluated using Chevallier's criteria, in which complete pathological response was defined as yT0yN0 or yTisN0. RESULTS: Thirty-nine eligible breast cancer patients treated with chemo-trastuzumab combined regimens in a neoadjuvant setting at Vietnam National Cancer Hospital were included in the analysis. Median age was 47 (range 32-72 years). Of these 39 patients, 5 (12.8%) were at stage II and 34 (87.2%) were at stage III. Median tumor size was 5.8 cm. There were 22 (56.4%) and 17 (43.6%) patients who had hormone receptor (HR) negative and positive diseases, respectively. Pathological complete response in the breast was demonstrated in 30 out of 39 (76.9%) patients. Of 35 patients with lymph nodal involvement, axillary pCR occurred in 25 (71.4%) patients. Total pathological complete response (tpCR) was achieved in 25 (64.1%) of the evaluated patients. There was no significant association between pathological response rates and age, tumor grade, hormone receptor status, and Ki-67 expression. CONCLUSION: Neoadjuvant treatment with trastuzumab and chemotherapy combined in patients with HER2 positive breast cancer yielded a pathological complete response rate of 64.1%.