A novel NSUN5/ENO3 pathway promotes the Warburg effect and cell growth in clear cell renal cell carcinoma by 5-methylcytosine-stabilized ENO3 mRNA.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) cells often reprogram their metabolisms. Enolase 3 (ENO3) is closely related to the Warburg effect observed in cells during tumor progression. However, the expression and function of ENO3 in ccRCC cells remain unclear. Therefore, this study investigated the expression and functional significance of ENO3 in the Warburg effect observed in ccRCC cells. METHODS: In this study, B-mode and microflow imaging ultrasound examinations were performed to evaluate patients with ccRCC. The extracellular acidification rate test and glucose uptake and lactate production assays were used to examine the Warburg effect in ccRCC cells. Western blotting, quantitative reverse transcription polymerase chain reaction, and immunochemistry were used to detect the expression of ENO3 and NOP2/Sun RNA methyltransferase 5 (NSUN5). RESULTS: ENO3 upregulation in ccRCC tumor tissues was accompanied by an increase in tumor size. Importantly, ENO3 participated in the Warburg effect observed in ccRCC cells, and high levels of ENO3 indicated a poor prognosis for patients. Loss of ENO3 reduced glucose uptake, lactate production, and extracellular acidification rate as well as inhibited ccRCC cell proliferation. Furthermore, NSUN5 was involved in the ENO3-regulated Warburg effect and ccRCC cell progression. Mechanically, NSUN5 was upregulated in ccRCC tissues, and NSUN5 upregulation mediated 5-methylcytosine modification of messenger RNA (mRNA) in ccRCC cells to promote mRNA stability and ENO3 expression. CONCLUSIONS: Collectively, the destruction of the NSUN5/ENO3 axis prevents ccRCC growth in vivo and in vitro, and targeting this pathway may be an effective strategy against ccRCC progression.

Regression of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: A case report.

BACKGROUND: Intervertebral disc calcification (IDC) combined with ossification of the posterior longitudinal ligament (OPLL) in cervical discs is rarely reported. This case study presents a rare case of IDC combined with OPLL in the C2-C3 segment. CASE SUMMARY: Here, we present a case of a 6-year-old Asian boy with severe neck pain and stiffness. Physical examination showed no neurological or other abnormalities. Digital radiography and computed tomography (CT) revealed a calcified intervertebral disc and OPLL at the C2-C3 vertebrae. The spinal canal compromise at C2-C3 was approximately 50% on magnetic resonance imaging. The final diagnosis was IDC combined with OPLL. We applied a neck brace for the patient to protect the neck. The patient's neck pain and stiffness recovered significantly within approximately 3 wk. At the 3 mo follow-up, the follow-up CT showed resolution of the ossified intervertebral disc herniation, and a small amount of calcification and slight OPLL remained at the involved segment. CONCLUSION: IDC combined with OPLL is a relatively rare condition in children. However, the majority of patients could have a favorable outcome, and the ossified mass in the canal would be spontaneously resolved with conservative therapy.

Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis.

BACKGROUND: The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA. METHODS: A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. RESULTS: Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks. CONCLUSION: The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed.

Bactericidal properties and biocompatibility of a gentamicin-loaded Fe3O4/carbonated hydroxyapatite coating.

Postoperative implant-associated infection remains a serious complication in total joint arthroplasty (TJA) surgery. The addition of antibiotics to bone cement is used as an antimicrobial prophylaxis in cemented joint arthroplasty; however, in cementless arthroplasty, there are no comparable measures for the local delivery of antibiotics. In this study, a gentamicin-loaded Fe3O4/carbonated hydroxyapatite coating (Gent-MCHC) was fabricated according to the following steps: (i) deposition of Fe3O4/CaCO3 particles on Ti6Al4V substrates by electrophoretic deposition; (ii) conversions of MCHC from Fe3O4/CaCO3 coatings by chemical treatment; and (iii) formation of Gent-MCHC by loading gentamicin into MCHC. MCHC possessed mesoporous structure with a pore size of about 3.8 nm and magnetic property with the saturation magnetization strength of about 4.03 emu/g. Gent-MCHC had higher drug loading efficiency and drug release capacity, and superior biocompatibility and mitogenic activity than Ti6Al4V. Moreover, Gent-MCHC deterred bacterial adhesion and prevented biofilm formation. These results demonstrate that Gent-MCHC can be used as a local drug delivery system to prevent implant-associated infection in TJA surgery.

[Color Doppler ultrasonic measurements of normal mesenteric lymph nodes in healthy children].

OBJECTIVE: To assess the value of color Doppler ultrasound in evaluating the mesenteric lymph nodes in healthy children. METHODS: The mesenteric lymph nodes were examined with color Doppler ultrasonography for 730 randomly selected healthy children under 14 years of age, including 410 boys and 298 girls who did not report any recent medical conditions. RESULTS: Abdominal lymph node detection rate was higher in boys than in girls. Abdominal lymph nodes were detected most often in children between the ages of 1 and 4 years, and the lymph node size decreased gradually with age. CONCLUSION: Color Doppler ultrasonography is valuable for evaluating abdominal lymph nodes in children.

[Enlarged mesenteric lymph nodes in children: a clinical analysis with ultrasonography and the implications].

OBJECTIVE: To compare the enlarged mesenteric lymph nodes in healthy children with those children with mesenteric lymphadenitis. METHODS: According to the diagnostic criteria defining lymph node enlargement as a 5-mm enlargement or greater in the short diameter, 137 healthy children and 148 children with mesenteric lymphadenitis were retrospectively analyzed for mesenteric lymph node enlargement based on the ultrasonographic data. RESULTS: The distribution of enlarged mesenteric lymph nodes was detected in the right lower quadrant (RLQ) in 46.3%, in the para-aortic areas in 19.2%, and in the left lower quadrant (LLQ) in 13.6% of the children. The clusters of lymph nodes between the two groups showed no significant difference in the distribution, age, L/W, longitudinal diameter or clusters, only the short diameter differed significantly between them. CONCLUSION: Enlarged mesenteric lymph nodes are present in many healthy children, which does not necessarily suggests any abnormalities. The mesenteric lymph nodes increase with the age until 6 years and then decrease. The lymph nodes with a short diameter larger than 8 mm may indicate the condition of mesenteric lymphadenitis.

[Preparation of transdermal drug delivery system of felodipine-metoprolol and its bioavailability in rabbits].

To prepare transdermal drug delivery system (TDDS) of felodipine and metoprolol and to study its pharmaceutical characteristics, pharmacokinetics and bioavailability in rabbits, an HPLC assay was established for the simultaneous determination of felodipine and metoprolol in the permeation receptor and patch. The permeation rate and permeation mechanism of felodipine-metoprolol-TDDS through rabbit skin in vitro was examined. The determination of drug content, the examination of content uniformity and stability of the TDDS were carried out. GC-ECD assays were established for the determination of felodipine and metoprolol in plasma separately and then employed to study the pharmacokinetics and bioavailability of felodipine and metoprolol after a single dose of oral or transdermal administration in rabbits. The results indicated that the permeation of flodipine and metoprolol from the patch through excised rabbit skin exhibited zero-order kinetic characteristics. The determination of drug content and the quality control of content uniformity of the patch accorded with Pharmacopoeia of the People's Republic of China of 2005 edition and the pharmaceutical characterization showed good stability. In contrast to oral delivery, relatively constant, sustained blood concentration with minimal fluctuation and prolonged peak time were observed over a long period after transdermal administration. The relative bioavailability of felodipine and metoprolol were 275.37% and 189.76% versus oral administration respectively. It was evident that the felodipine-metoprolol-TDDS exhibited good controlled release properties that satisfied the demands of original design that enhancing bioavailability and maintaining appropriate blood levels for a prolonged time without adverse effects associated with frequent oral administration.