Curcuma Longa Induces the Transcription Factor FOXP3 to Downregulate Human Chemokine CCR5 Expression and Inhibit HIV-1 Infection.

HIV mutations occur frequently despite the substantial success of combination antiretroviral therapy, which significantly impairs HIV progression. Failure to develop specific vaccines, the occurrence of drug-resistant strains, and the high incidence of adverse effects due to combination antiviral therapy regimens call for novel and safer antivirals. Natural products are an important source of new anti-infective agents. For instance, curcumin inhibits HIV and inflammation in cell culture assays. Curcumin, the principal constituent of the dried rhizomes of Curcuma longa L. (turmeric), is known as a strong anti-oxidant and anti-inflammatory agent with different pharmacological effects. This work aims to assess curcumin's inhibitory effects on HIV in vitro and to explore the underpinning mechanism, focusing on CCR5 and the transcription factor forkhead box protein P3 (FOXP3). First, curcumin and the RT inhibitor zidovudine (AZT) were evaluated for their inhibitory properties. HIV-1 pseudovirus infectivity was determined by green fluorescence and luciferase activity measurements in HEK293T cells. AZT was used as a positive control that inhibited HIV-1 pseudoviruses dose-dependently, with IC50 values in the nanomolar range. Then, a molecular docking analysis was carried out to assess the binding affinities of curcumin for CCR5 and HIV-1 RNase H/RT. The anti-HIV activity assay showed that curcumin inhibited HIV-1 infection, and the molecular docking analysis revealed equilibrium dissociation constants of [Formula: see text]9.8[Formula: see text]kcal/mol and [Formula: see text]9.3[Formula: see text]kcal/mol between curcumin and CCR5 and HIV-1 RNase H/RT, respectively. To examine curcumin's anti-HIV effect and its mechanism in vitro, cell cytotoxicity, transcriptome sequencing, and CCR5 and FOXP3 amounts were assessed at different concentrations of curcumin. In addition, human CCR5 promoter deletion constructs and the FOXP3 expression plasmid pRP-FOXP3 (with an EGFP tag) were generated. Whether FOXP3 DNA binding to the CCR5 promoter was blunted by curcumin was examined using transfection assays employing truncated CCR5 gene promoter constructs, a luciferase reporter assay, and a chromatin immunoprecipitation (ChIP) assay. Furthermore, micromolar concentrations of curcumin inactivated the nuclear transcription factor FOXP3, which resulted in decreased expression of CCR5 in Jurkat cells. Moreover, curcumin inhibited PI3K-AKT activation and its downstream target FOXP3. These findings provide mechanistic evidence encouraging further assessment of curcumin as a dietary agent used to reduce the virulence of CCR5-tropic HIV-1. Curcumin-mediated FOXP3 degradation was also reflected in its functions, namely, CCR5 promoter transactivation and HIV-1 virion production. Furthermore, curcumin inhibition of CCR5 and HIV-1 might constitute a potential therapeutic strategy for reducing HIV progression.

Various presentations of fourth branchial pouch sinus tract during surgery.

CONCLUSION: A recurrent neck abscess or acute suppurative thyroiditis should arouse suspicion of fourth branchial pouch sinus. Complete surgical excision is usually curative. The classification of sinus tract according to the area where it is emerging from the larynx may be helpful in identifying the tract during surgery. OBJECTIVE: To describe our experience of the diagnosis and management of fourth branchial pouch sinus and elucidate three different emerging pathways of the sinus tract during surgery. METHODS: Retrospective case series with eight patients who were diagnosed with fourth branchial pouch sinus between January 2007 and July 2011 at the First Affiliated Hospital of Zhengzhou University. RESULTS: Six patients presented with recurrent neck abscess, two presented with acute suppurative thyroiditis. All patients had barium swallow and sinus tract was delineated in six cases. All eight patients underwent surgical excision of the sinus tract. Three different emerging pathways of the sinus tract were identified during surgery. The tract could penetrate the thyroid cartilage near the inferior horn, the inferior pharyngeal constrictor muscle or the cricothyroid membrane when it emerged from the larynx. The recurrent laryngeal nerve was commonly dissected to avoid inadvertent damage. Hemithyroidectomy was performed in six patients. All eight are currently asymptomatic.

[Diagnosis and management of congenital pyriform sinus fistula].

OBJECTIVE: To explore the clinical presentation and management principles of congenital pyriform sinus fistula. METHODS: Seven sequential cases of congenital pyriform sinus fistula (CPSF) treated between January 2007 and January 2011 were reported. The clinical presentation were recurrent left lower neck abscess or acute suppurative thyroiditis. All of these patients had past histories of misdiagnosis ranged from 3 years to 11 years. All the patients had undergone incision and drainage several times. In acute infection period, these patients received incision and drainage, after inflammation subsided, were treated with definitive surgery. RESULTS: After barium swallow study and CT examination in the quiescent stage of infection, 5 patients could be seen fistula in the pyriform, all the patients were found scar tissue near the left thyroid lobe, 4 patients received direct laryngoscope examination and 3 of them could be found inner orifice near the apex of pyriform sinus, fistula and the involved lobe of thyroid were successfully excised without permanent recurrent laryngeal nerve injury or hypothyroidism. All the patients had an uneventful recovery and remained symptom free from 5 months to 40 months. CONCLUSIONS: The clinical history of recurrent low neck inflammatory episodes in patients, especially on the left side, should raise the suspicion of CPSF, investigation using barium swallow in combination with CT scanning is useful. CPSF can be treated by excising the fistula and involved lobe of thyroid.

[Glossopharyngeal neurotomy through laterocervical approach to treat idiopathic glossopharyngeal neuralgia].

OBJECTIVE: To introduce a modified laterocervical approach for glossopharyngeal neurotomy to treat idiopathic glossopharyngeal neuralgia. METHODS: The clinical data, the operative technique, the operative effects and (the results of) follow-up of 12 patients were presented. Through reviewing pertinent literatures, the therapeutic advancement of glossopharyngeal neuralgia and the modified technique of laterocervical approach for glossopharyngeal neurotomy were discussed. New idea on operations, of which the use of insulation coverings when cauterizing the inferior ganglion of glossopharyngeal nerve and Jacobson nerve were brought. Homonymous superior laryngeal nerve was excised at the same time. RESULTS: All patients (the cases) were followed-up for 3 months to 3 years with an median of 15 months. Among the 12 patients suffered from glossopharyngeal neuralgia, 11 patients were satisfied with the outcomes and remained disease free after surgical treatment. The remission rate of pain was 100.0%, complete remission rate of pain was 91.7%. Only a few patients had complications. Intraoperative leakage of cerebrospinal fluid was obstructed with gelatin sponge and pasted with mucilage in 1 case and no complication appeared in the convalescence stage. Postoperatively, facial palsy was found in 1 case which was self-cured after a week, postoperative voice depression in 1 case, and foreign body sensation in 2 cases. CONCLUSIONS: Laterocervical approach for glossopharyngeal neurotomy is an available method to treat idiopathic glossopharyngeal neuralgia.