Genetic background of neonatal hypokalemia.

Neonatal hypokalemia (defined as a serum potassium level <3.5 mEq/L) is the most common electrolyte disorder encountered in clinical practice. In addition to common secondary causes, primary genetic etiologies are also closely associated with hypokalemia. Currently, a systematic characterization of these genetic disorders is lacking, making early recognition challenging and clinical management uncertain. This review will aid clinicians by summarizing the genetic background of neonatal hypokalemia from two aspects: (1) increased excretion of K+, whereby genetic factors primarily lead to increased renal Na+ influx, decreased H+ efflux, or reduced Cl- influx, ultimately resulting in increased K+ efflux; and (2) decreased extracellular distribution of K+, whereby genetic factors result in abnormalities in transmembrane ion channels, reducing outward potassium currents or generating inward cation leak currents. We describe over ten genetic diseases associated with neonatal hypokalemia, which involve pathogenic variants in dozens of genes and affect multiple target organs, including the kidneys, intestines, and skeletal muscle. For example, in the renal tubules, pathogenic variants in the SLC12A1 gene encoding the Na+-K+-2Cl- cotransporter lead to renal K+ loss, causing Bartter syndrome type I; in intestinal epithelial cells, pathogenic variants in the SLC26A3 gene result in a defective Cl⁻-HCO3⁻ exchanger, causing congenital chloride diarrhea; and in skeletal muscle, pathogenic variants in the CACNA1S gene impact membrane calcium ion channels resulting in hypokalemic periodic paralysis. Given the wide variety of organs and genetic alterations that can contribute to neonatal hypokalemia, we believe this review will provide valuable insights for clinical diagnosis and treatment.

Genotype and phenotype features and prognostic factors of neonatal-onset pyridoxine-dependent epilepsy: A systematic review.

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a rare autosomal recessive disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase. This study aimed to systematically explore genotypic and phenotypic features and prognostic factors of neonatal-onset PDE. A literature search covering PubMed, Elsevier, and Web of Science was conducted from January 2006 to August 2023. We identified 56 eligible studies involving 169 patients and 334 alleles. The c.1279 G>C variant was the most common variant of neonatal-onset PDE (25.7 %). All patients were treated with pyridoxine; forty patients received dietary intervention therapy. 63.9 % of the patients were completely seizure-free; however, 68.6 % of the patients had neurodevelopmental delays. Additionally, homozygous c.1279 G>C variants were significantly associated with ventriculomegaly, abnormal white matter signal, and cysts (P<0.05). In contrast, homozygous c.1364 T>C was associated with clonic seizure (P=0.031). Pyridoxine used immediately at seizure onset was an independent protective factor for developmental delay (P=0.035; odds ratio [OR]: 3.14). Besides, pyridoxine used early in the neonatal period was a protective factor for language delay (P=0.044; OR: 4.59). In contrast, neonatal respiratory distress (P=0.001; OR: 127.44) and abnormal brain magnetic resonance imaging (P=0.049; OR: 3.64) were risk factors. Prenatal movement abnormality (P=0.041; OR: 20.56) and abnormal white matter signal (P=0.012; OR: 24.30) were risk factors for motor delay. Myoclonic seizure (P=0.023; OR: 7.13) and status epilepticus (P=0.000; OR: 9.93) were risk factors for breakthrough seizures. In conclusion, our study indicated that pyridoxine should be started immediately when unexplained neonatal seizures occur and not later than the neonatal period to prevent poor neurodevelopmental outcomes.

Characterization and in vitro simulated gastrointestinal digestion and fermentation of Mentha haplocalyx polysaccharide.

An acidic polysaccharide (PMHP-3) obtained from the Mentha haplocalyx was structurally characterized, and in vitro simulated digestion and fermentation were investigated. PMHP-3 was mainly composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose with molecular weight of 21.82 kDa. After digestion in saliva and simulated gastric juice, the molecular weight, reducing sugar, total sugar and uronic acid contents of PMHP-3 did not change significantly (p > 0.05). After digestion in simulated intestinal juice, the molecular weight and uronic acid content of PMHP-3 did not change significantly, and there was no free monosaccharide production, but the total sugar and reducing sugar contents slightly decreased. During fermentation, the molecular weight, carbohydrate residue and free monosaccharides of PMHP-3 were decreased, suggesting that PMHP-3 could be degraded by microorganism and metabolized into a variety the short-chain fatty acids (SCFAs) such as acetic, propionic. Meanwhile, PMHP-3 modulated the gut microbiota by reducing the ratio of Firmicutes/Bacteroidetes, promoting the proliferation of beneficial bacteria such as Bacteroidaceae and Bifidobacteriaceae, and inhibiting harmful bacteria such as Lachnospiraceae and Enterobacteriaceae. These results indicate that PMHP-3 is beneficial to the gut health and can be developed as a potential prebiotic to prevent diseases by improving intestinal health.

Comparison on characterization and biological activities of Mentha haplocalyx polysaccharides at different solvent extractions.

This study aimed to compare the effects of four solvent extractions on the physicochemical properties, antioxidant and hypoglycemic activities of polysaccharides from Mentha haplocalyx (MHPs). The solvent extractions included hot water, citric acid (pH 3.0), 5% NaOH/0.05% NaBH4 and 0.9% NaCl. Four corresponding MHPs named as MHP-W, MHP-C, MHP-A and MHP-S were obtained, respectively. The experimental results showed that the extraction yields, basic chemical components, monosaccharide contents, molecular weights, antioxidant and hypoglycemic activities of four MHPs were significantly different. However, their thermal stabilities, preliminary structural characteristics and monosaccharide types were similar. MHP-A possessed the highest extraction yield of 9.37 ± 0.24% and the smallest molecular weight. MHP-W had the highest uronic acid content and the largest molecular weight. More specifically, MHP-C exhibited the highest sugar content, the most remarkable antioxidant abilities of DPPH radical scavenging activity and ferric reducing power, and the strongest inhibitory activities on α-glucosidase and α-amylase. The above results indicated that MHP-C extracted with citric acid could be served as a promising bioactive substance for applications in the functional food and medicine industries.

Comparison of different extraction methods for polysaccharides from bamboo shoots (Chimonobambusa quadrangularis) processing by-products.

The aim of this study was to evaluate the influences of extraction methods on the yield, chemical structure and antioxidant activity of polysaccharides from bamboo shoots (Chimonobambusa quadrangularis) processing by-products (CPS). CPSs were extracted by using five methods including hot water extraction (HWE), accelerated solvent extraction (ASE), ultrasonic-assisted extraction (UAE), microwave-assisted extraction (MAE) and enzyme-assisted extraction (EAE). The experimental results showed that the uronic acid contents, monosaccharide contents, molecular weights and antioxidant activities of the five CPSs were significantly different. CPS extracted using ASE method (ASE-CPS) possessed the highest extraction yield (9.94%), the highest medium-high-molecular-weight value (136.07 kDa) and notable antioxidant ability. UAE-CPS had the highest uronic acid (9.42%) and the lowest medium-high-molecular weight value (117.49 kDa), and its antioxidant activity was the best. Based on the correlation analysis, the higher uronic acid content, smaller molecular weight, and lower content of monosaccharide composition of glucose for the CPS-UAE might contribute to its higher antioxidant activity. From an industrial viewpoint, ASE technique could be a promising and alternative way to extract CPS due to its high yield, notable antioxidant activity, and convenient industrialization.