[Research progress in N6-methyladenosine modification in the field of stomatology].

N6-methyladenosine (m6A) is the most abundant and widely distributed internal RNA modification in eukaryotic cells, and it is involved in the regulation of gene expression and biological processes in many cells. In recent years, studies on the role of m6A modification in oral cavity have emerged gradually. Existing researches show that m6A-related proteins are involved in the regulation of oral squamous cell carcinoma and its resistance to therapy. Methyltransferase-like 3 regulates apoptosis and autophagy of chondrocytes in inflammation, the angiogenesis and osteogenesis during distraction osteogenesis of endothelial progenitor cells, inflammatory response of dental pulp cells, the differentiation and osteogenesis of dental pulp stem cells, the development of tooth roots and the differentiation of bone marrow mesenchymal stem cells and so on. Moreover, m6A modification may also be related to the occurrence and development of periodontitis, oral ulcers and oral submucosal fibrosis. These studies have provided new ideas for the pathogenesis of various oral diseases and the diagnosis and treatment of oral bone tissue repair and regeneration. This paper reviews the recent research progress on the role of m6A modification in the field of stomatology and summarize the current research status of m6A in the field of stomatology, in order to provide reference for the further research of m6A function and mechanism in the field of stomatology.

[Research progress of topical treatment of oral chronic graft versus host disease: a review].

Oral cavity is one of the main organs involved in chronic graft versus host disease (cGVHD). Oral cGVHD seriously affects the patient's quality of life. Topical use of glucocorticoid and other agents is the primary topical treatment of oral cGVHD, oral photochemical therapy and various new methods have also been applied in patients recently. These important adjuvant therapies are based on the systemic use of drugs such as immunosuppressive agents, and sometimes, may be the only effective treatment for oral cGVHD. This review will focus on the application of topical agent treatment and oral photochemotherapy in oral cGVHD patients.

Intravenous hyperalimentation with high arginine levels improves wound healing and immune function.

The purpose of this study was to evaluate the effect of increased arginine levels in intravenous hyperalimentation (IVH) therapy on wound healing and thymic immune function. Groups of SD rats, 275-325 g, underwent placement of internal jugular catheter, 7-cm dorsal skin wounding, insertion of polyvinyl alcohol sponges subcutaneously, and closure of wounds with stainless-steel sutures. Twenty-four hours later, rats were started on IVH at a rate of 0.8-1 ml/100 g body wt/hr. All IVH solutions contained 20% dextrose, adequate amounts of minerals and vitamins, and two different amino acid mixtures: (A) Fre III (4.05 g ARG/liter) (n = 13); (B) experimental (7.50 g ARG/liter) (n = 11). Solutions were isonitrogenous, and contained similar amounts of essential amino acids. After 7 days of IVH, weight gain did not differ between the two groups; however, cumulative N balance was superior in group A. Wound healing was improved in group B as assessed by fresh wound strip breaking strength, fixed breaking strength, and the amount of reparative collagen deposition as assessed by the hydroxyproline content of the implanted sponges. Group B animals also had improved thymic function as assessed by thymic weight, the total number of thymic lymphocytes/gland and mitogenic reactivity of thymic lymphocytes to PHA and Con A. The experiments indicate that high arginine levels in IVH solutions improve wound healing and thymic immune function following injury.

Optimal levels of arginine in maintenance intravenous hyperalimentation.

The optimal levels of arginine (Arg) for growth and immunity were studied in mildly depleted, noninjured rats maintained on intravenous hyperalimentation. Three groups of S-D rats (eight/group, weighing 275-300 g) underwent catheter insertion, 1 day of fasting, and then 7 days of intravenous hyperalimentation consisting of 20% dextrose, adequate minerals and vitamins, and three amino acid regimens: (1) FreAmine II (1.55 g Arg/liter); (2) FreAmine III (4.05 g Arg/liter); (3) experimental (7.5 g Arg/liter). The increase in arginine levels was achieved by lowering the glycine levels. There were no differences among the groups in terms of body weight gain (6.9 vs 8.3 vs 10.0 g) or in cumulative N balance (574 vs 660 vs 642 mg). Liver, spleen, and adrenal weights did not differ. Thymus weight was greater in groups B and C: (A) 345 +/- 27 mg vs (B) 445 +/- 34 mg, p less than 0.05, vs (C) 438 +/- 26 mg, p less than 0.05) as were the total number of lymphocytes/thymus (X 10(-9) (A) 0.93 +/- 0.12 vs (B) 1.37 +/- 0.18, p less than 0.05, vs (C) 1.46 +/- 0.15, p less than 0.05). Mitogen-induced thymocyte blastogenesis (cpm) was greatest in group C in response to phytohemagglutinin: (A) 9.558 +/- 3,799 vs (B) 20,088 +/- 5,890, NS, vs (C) 37,234 +/- 6,209, p less than 0.01 vs A and p less than 0.05 vs B) and Concanavalin A: (A) 71,035 +/- 15,228 vs (B) 111,734 +/- 15,021, NS, vs (C) 172,967 +/- 19,861, p less than 0.01 vs A and p less than 0.05 vs B). In the intravenous hyperalimentation-maintained noninjured rat ARG concentrations more than 1.55 g/liter do not enhance N retention or growth. Larger doses of ARG have strong thymic immunostimulatory effects without any toxicity or growth reduction.

Effect of carnitine on liver fat and nitrogen balance in intravenously fed growing rats.

Carnitine is an essential metabolite whose function is to transport activated long-chain fatty acids across the mitochondrial membrane. It is consumed in the diet and is synthesized from lysine and methionine to meet body needs. Hepatic fat deposition has been reported in experimental animals and patients receiving total parenteral nutrition (TPN) fluids devoid of preformed carnitine. In the present experiment, nitrogen balance, hepatic fat deposition and serum and tissue carnitine were determined in rats receiving a hypercaloric TPN regimen containing 0, 10, 50, and 100 mg DL-carnitine per 100 g body weight for 14 days. Rats fed a stock diet served as controls. Increased nitrogen balance was observed in TPN rats receiving the highest dose of carnitine supplementation. Hepatic fat deposition induced by the hypercaloric infusion was ameliorated but not eliminated by infusing carnitine. Serum, liver and skeletal muscle carnitine concentrations were maintained, whereas that of heart decreased in TPN rats without carnitine supplementation. Between 90 and 100% of the administered L-carnitine was excreted. It is suggested that the observed effects of carnitine on nitrogen balance and hepatic fat deposition are due to as yet undefined pharmacological properties. The significant decrease of carnitine in cardiac muscle resulting from TPN in a patient population already stressed and traumatized and the metabolic and physiological effects of this decrease deserve further exploration.

Determination of intravenous non-protein energy and nitrogen requirements in growing rats.

Two experiments were conducted to estimate total non-protein energy and nitrogen requirements in growing healthy male Wistar rats nourished by parenteral nutrition. In experiment 1, non-protein energy varying from 30 to 70 kcal/day/rat were administered to animals receiving a constant dose of 80 mg nitrogen, plus vitamins and minerals. In experiment 2, nitrogen dosages varying from 0 to 280 mg N/day/rat with a constant dose of 60 kcal non-protein energy were studied. The formulation of the amino acid solution used in both experiments was based upon recommended oral amino acid requirements for growing rats. Dextrose served as the source of non-protein energy. Weight gain and nitrogen balance during a 6-day experimental period were used to determine requirements. Plasma free amino acids were also analyzed to evaluate the amino acid solution. Results indicate that under total parenteral nutrition conditions 578 to 621 mg/kg body weight3/4 nitrogen and 171 to 182 kcal/kg body weight3/4 non-protein energy are required to achieve growth of approximately 3 g/day. Inconsistent responses of plasma amino acid concentrations to the amounts infused were observed. It is suggested that the determined requirements can be applied as guidelines to research using the rat as an animal model in total parenteral nutrition.

Protein-sparing effect of intravenously administered branched chain amino acids in adult rats.

Branched chain amino acids (BCAA) serve as intermediate energy substrates for peripheral tissues. Experiments were conducted to evaluate protein-sparing properties of BCAA at different doses without dextrose. Forty healthy male adult Wistar rats, weighing 437 +/- 34 gm, were randomly assigned to one of five groups. Four groups of eight rats were cannulated at the jugular vein and infused with 3% amino acid solutions containing 13, 23, 50 or 100% BCAA; an additional eight fasted rats served as controls. Results show that weight loss was not significantly different between groups, but was lower than in the fasted rats. Nitrogen balance (NB) was least negative in the 23% BCAA group, followed by 13, 50 and 100% BCAA. Protein-sparing index (PSI), defined as that portion of the infused nitrogen that is used for sparing body proteins, agreed with the calculated fat/protein ratios. Higher PSI and fat/protein ratios resulted from solutions containing balanced amino acid patterns (13 and 23%). No obvious imbalances in plasma amino acid patterns were observed. It is concluded that more protein conservation can be achieved with amino acid solutions containing a balanced amino acid pattern and that the effect of additional BCAA on protein conservation is limited in adult rats.

The metabolism of the isomeric tert.-butylcyclohexanones.

1. (+/-)-2-, (+/-)-3- and 4-tert.-Butylcyclohexanone are reduced in the rabbit to secondary alcohols, which are excreted extensively conjugated with glucuronic acid. 2. The major metabolite of (+/-)-2-tert.-butylcyclohexanone is (+)-cis-2-tert.-butylcyclohexanol, which has been isolated from the urine as [(+)-cis-2-tert.-butylcyclohexyl beta-d-glucosid]uronic acid. The minor metabolite is (+)-trans-2-tert.-butylcyclohexanol. 3. (+/-)-3-tert.-Butylcyclohexanone is reduced mainly to (+/-)-cis-3-tert.-butylcyclohexanol, and to a smaller extent to (+/-)-trans-3-tert.-butylcyclohexanol. 4. 4-tert.-Butylcyclohexanone yields mainly the trans-alcohol, which is excreted in conjugated form and has been recovered from the urine as (trans-4-tert.-butylcyclohexyl beta-d-glucosid)uronic acid. The cis-alcohol is formed to a minor extent and excreted in conjugated form. 5. The ratios of the amounts of cis- to trans-alcohols produced by the three ketones differed from the relative amounts of cis- and trans-alcohols produced by the corresponding methylcyclohexanones. 6. From these findings the suggestion is made that two orientations of ketone relative to coenzyme occur: alcohols with an equatorially orientated hydroxyl group are thought to be produced as a result of a ;face-to-face' interaction with NADH, and alcohols with axially orientated hydroxyl groups as a result of a ;perpendicular' interaction. Which will predominate is thought to depend on steric factors, particularly the size and position of alkyl substituents in the substrate.