Alashanines A-C, Three Quinone-Terpenoid Alkaloids from Syringa pinnatifolia with Cytotoxic Potential by Activation of ERK.

Three quinone-terpenoid alkaloids, alashanines A-C (1-3), possessing an unprecedented 6/6/6 tricyclic conjugated backbone and quinone-quinoline-fused characteristic, were isolated from the peeled stems of Syringa pinnatifolia. Their structures were elucidated by analysis of extensive spectroscopic data and quantum chemical calculations. A hypothesis of biosynthesis pathways for 1-3 was proposed on the basis of the potential precursor iridoid and benzoquinone. Compound 1 exhibited antibacterial activities against Bacillus subtilis and cytotoxicity against HepG2 and MCF-7 human cancer cell lines. The results of the cytotoxic mechanism revealed that compound 1 induced apoptosis of HepG2 cells through activation of ERK.

Analysis of 70 patients with hydrocephalus due to cobalamin C deficiency.

OBJECTIVE: To analyze the clinical characteristics of patients with hydrocephalus secondary to cobalamin C (cblC) deficiency and to discuss the optimal strategies for assessing and treating such patients by performing clinical and laboratory studies in 70 patients. METHODS: A total of 1,211 patients were clinically diagnosed with methylmalonic acidemia (MMA) from 1998 to 2019. Among them, cblC deficiency was confirmed in 70 patients with hydrocephalus by brain imaging and biochemical and genetic analysis. RESULTS: Of the 70 patients, 67 (95.7%) had early-onset MMA and homocystinuria. The patients typically had high blood propionylcarnitine and total homocysteine, low methionine, and methylmalonic aciduria. Signs of intracranial hypertension were relatively rare. We measured ventricular dilatation early in the disease by cranial ultrasound and MRI and/or CT. Eighteen different MMACHC mutations, including 4 novel mutations (c.427C>T, c.568insT, c.599G>A, and c.615C>A), were identified biallelically in all 70 patients. c.609G>A was the most frequent mutation, followed by c.658_660del, c.217C>T, and c.567dupT. Three cases were diagnosed by postmortem study. Metabolic therapy, including cobalamin injections supplemented with oral l-carnitine and betaine, was administered in the remaining 67 cases. A ventriculoperitoneal shunt was performed in 36 cases. During the follow-up, psychomotor development, nystagmus, impaired vision, and sunset eyes improved gradually. CONCLUSION: Hydrocephalus is a severe condition with several different causes. In this study, ventriculomegaly was found in 70 patients with cblC deficiency. Early diagnosis, etiologic treatment, and prompt surgical intervention are crucial to improve the prognosis of patients.

[Chemical and pharmacological progress on a Tibetan folk medicine formula Bawei Chenxiang Powder].

Bawei Chenxiang Powder is a traditional Tibetan folk medicine formula, consisting of resinous wood of Aquilaria sinensis, kernel of Myristica fragrans, fruit of Choerospondias axillaris, travertine, resin of Boswellia carterii or B. bhaw-dajiana, stem of Aucklandia lappa, fruit of Terminalia chebula(roasted), and flower of Gossampinus malabarica. It has the function of clearing heart heat, nourishing heart, tranquilizing mind, and inducing resuscitation, which has been used for the treatment of coronary heart disease and angina pectoris. Modern research shows that the medicine materials of this formula mainly contain terpenoids like sesquiterpenes and triterpenes and polyphenols like flavonoids, lignans, and tannins, displaying some pharmacological activities such as anti-myocardial ischemia, anti-cerebral ischemia, and spatial learning and memory promotion. This review summaries the traditional uses, chemical constituents, and pharmacological activities research progress, hopefully to provide a reference for clarification of its pharmacological active ingredients.

Patients with cobalamin G or J defect missed by the current newborn screening program: diagnosis and novel mutations.

Cobalamin G (cblG) and cobalamin J (cblJ) defects are rare disorders of cbl metabolism caused by MTR and ABCD4 mutations, respectively. Patients with atypical biochemical features can be missed by current newborn screening using tandem mass spectrometry (MS/MS), in which total homocysteine (tHCY) in dried blood spots (DBS) is not a primary biomarker. Two Chinese patients suspected of cbl defect but missed by newborn screening were studied. Using comprehensive metabolic analyses including MS/MS assay for tHCY in DBS, slightly low methionine in Patient 1, methymalonic aciduria in Patient 2, and homocysteinemia in both patients were detected, and DBS tHCY of two patients were obviously elevated (59.22 µmol/L, 17.75 µmol/L) compared to 140 healthy controls (2.5th-97.5th percentile, 1.05-8.22 µmol/L). Utilizing whole-exome sequencing, we found two novel MTR variants c.871C>T (p.Pro291Ser) and c.1771C>T (p.Arg591*) in Patient 1, and a ABCD4 homozygous variant c.423C>G (p.Asn141Lys) in Patient 2. Our study identified the first cblG patient and cblJ patient in mainland China, and highlighted comprehensive metabolic analyses and genetic tests in patients suspected of cbl defects. It also indicated that supplementary MS/MS assay for tHCY in DBS may be practical for early diagnosis of homocysteinemia, without repeated blood sampling.