Case Report and Review of Literature: Autosomal Recessive Hypophosphatemic Rickets Type 2 Caused by a Pathogenic Variant in ENPP1 Gene.

Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hereditary rickets, which is characterized by defective bone mineralization and renal phosphate wasting due to a loss-of-function variant in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene. Although pathogenic variant of ENPP1 has been known to manifest other phenotypes including arterial calcification, hearing loss, ossification of posterior longitudinal ligament, or pseudoxanthoma elasticum, there have been few reports including systematic examination in individuals diagnosed with ARHR2 to date. Herein, we report a case of ARHR2 with a bi-allelic pathogenic variant of ENPP1, in which the patient presented with gait abnormalities with severe genu varum at 26 months of age. Targeted gene panel sequencing was performed to investigate the genetic cause of rickets, and a homozygous nonsense variant in ENPP1, c.783C>G (p.Tyr261*), was identified. The patient was treated with oral phosphate and active vitamin D supplements and underwent corrective osteotomy for varus deformity. His phenotype was limited to rickets. A periodic systematic evaluation is needed to identify any comorbidities in ARHR2 patients since ENPP1 variants may present phenotypes other than rickets and symptoms may evolve or change over time.

Infant with early onset bilateral facial and bulbar weakness: Successful treatment of riboflavin in multiple acyl-CoA dehydrogenase deficiency caused by biallelic nonsense FLAD1 variants.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a heterogeneous group of inborn error of metabolic disease affecting the oxidation of fatty acids and amino acids, and choline metabolism. Genes involved in electrons transfer to the mitochondrial respiratory chain typically induce MADD. Recently, FLAD1, which encodes flavin adenine dinucleotide synthase, has also been reported as a cause of MADD. Here, we present a case of a 28-month girl with progressive weakness in facial and bulbar muscle. She has been suffering from feeding difficulty and recurrent respiratory distress. Lipid storage myopathy was evident from muscle biopsy. Furthermore, whole exome sequencing identified homozygous variant of c.745C > T (p.Arg249*) in FLAD1, confirming the diagnosis of FLAD1-related MADD. The patient showed improvements in her symptoms and exhibited catch-up growth following the supplementation of riboflavin. Lipid storage myopathy with FLAD1-related MADD is potentially treatable. Therefore, we should have high clinical suspicion, even though the diagnosis is challenging.

Evaluation of the antioxidant activities and nutritional properties of ten edible plant extracts and their application to fresh ground beef.

In this study, we assessed the antioxidant efficacy and nutritional value of 10 leafy edible plants and evaluated their potential as natural antioxidants for meat preservation. We measured total phenolic content, 2,2-diphenyl-1-picryl-hydrazil (DPPH) radical scavenging activity, and vitamin C, chlorophyll, and carotenoid contents of 70% ethanol and water extracts of the edible plants. Based on these results, we investigated the effects of butterbur and broccoli extracts on lipid oxidation in ground beef patties. Plant extracts and butylated hydroxytoluene (BHT) were individually added to patties at both 0.1% and 0.5% (w/w) concentrations. Thiobarbituric acid reactive substance (TBARS) values and color parameters were tested periodically during 12 days of refrigerated storage. TBARS levels were significantly lower (p≤0.05) in the samples containing plant extracts or BHT than the non-treated control. In addition, the beef patties formulated with the selected plant extracts showed significantly (p≤0.05) better color stability than those without antioxidants. These results indicate that edible plant extracts are promising sources of natural antioxidants and can potentially be used as functional preservatives in meat products.

Endothelial NO/cGMP-dependent vascular relaxation of cornuside isolated from the fruit of Cornus officinalis.

Cornuside is a bisiridoid glucoside compound isolated from the fruit of CORNUS OFFICINALIS Sieb. et Zucc. (Cornaceae). In the present study, we investigated the effect of cornuside on vascular tone in rat aortic tissue. Cornuside induced a concentration-dependent relaxation of the phenylephrine-precontracted rat aorta, which was abolished by removal of the endothelial layer. Pretreatment of the aortic tissues with either N(G)-nitro- L-arginine methyl ester (L-NAME) or 1 H- -oxadiazole-[4,3-alpha]-quinoxalin-1-one (ODQ) completely inhibited the relaxation induced by cornuside. However, the relaxant effect of cornuside was not blocked by pretreatment with verapamil, diltiazem, tetraethylammonium (TEA), glibenclamide, indomethacin, atropine, or propranolol. In addition, incubation of human umbilical vein endothelial cells (HUVECs) with cornuside increased the production of cGMP in a dose-dependent manner, but this effect was blocked by pretreatment with L-NAME and ODQ, respectively. Taken together, the present study suggests that cornuside dilates vascular smooth muscle via endothelium-dependent nitric oxide (NO)/cGMP signaling.

Pharmacological activity in growth inhibition and apoptosis of cultured human leiomyomal cells of tropical plant Scutellaria barbata D. Don (Lamiaceae).

Scutellaria barbata D. Don (Lamiaceae) (SB), which is known in traditional Korean medicine, has been used as an anti-inflammatory and antitumor agent. Since uterine leiomyoma is the most common benign smooth muscle cell tumor of the myometrium, we aimed to determine the growth inhibition and the induction of apoptotic cell death brought about by the herb SB in two different leiomyomal cells, named LM-1 and LM-2, and to clarify the mechanism of this apoptosis. Water-soluble ingredients of SB, and the leiomyomal cell lines of LM-1 and LM-2, were used in vitro. Growth inhibition, induction of cell death, morphological features, the presence of DNA ladders, increases in Caspase 3-like activity, the effects of a Caspase 3 inhibitor on apoptotic cell death, and the release of Cytochrome C by SB were analyzed. SB inhibited the growth and decreased the viability of the leiomyomal cells. The viability of normal myomatrial smooth muscle cells (SMC) in the presence of low concentrations of SB was higher than those of leiomyomal cells. Apoptotic bodies and DNA ladders were observed to be induced in leiomyomal cells of LM-1 and LM-2 by SB. The synthetic tetrapeptide Caspase 3 inhibitor, N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), inhibited the apoptotic cell death of leiomyomal cells induced by SB. The Caspase 3-like activity in leiomyomal cells LM-1 and LM-2 increased after the addition of SB. Cytochrome C was released from mitochondria into the cytosol 8h after the addition of SB, and reached a peak at 16h. The peak of Cytochrome C release was earlier than that of Caspase 3-like activity. We concluded that SB inhibited the growth of the leiomyomal cells and induced apoptosis. The apoptosis of leiomyomal cells induced by SB was associated with the release of Cytochrome C from the mitochondria, followed by an increase in Caspase 3-like activity.