Photodynamic O2 Economizer Encapsulated with DNAzyme for Enhancing Mitochondrial Gene-Photodynamic Therapy.

Emerging research suggests that mitochondrial DNA is a potential target for cancer treatment. However, achieving precise delivery of deoxyribozymes (DNAzymes) and combining photodynamic therapy (PDT) and DNAzyme-based gene silencing together for enhancing mitochondrial gene-photodynamic synergistic therapy remains challenging. Accordingly, herein, intelligent supramolecular nanomicelles are constructed by encapsulating a DNAzyme into a photodynamic O2 economizer for mitochondrial NO gas-enhanced synergistic gene-photodynamic therapy. The designed nanomicelles demonstrate sensitive acid- and red-light sequence-activated behaviors. After entering the cancer cells and targeting the mitochondria, these micelles will disintegrate and release the DNAzyme and Mn (II) porphyrin in the tumor microenvironment. Mn (II) porphyrin acts as a DNAzyme cofactor to activate the DNAzyme for the cleavage reaction. Subsequently, the NO-carrying donor is decomposed under red light irradiation to generate NO that inhibits cellular respiration, facilitating the conversion of more O2 into singlet oxygen (1 O2 ) in the tumor cells, thereby significantly enhancing the efficacy of PDT. In vitro and in vivo experiments reveal that the proposed system can efficiently target mitochondria and exhibits considerable antitumor effects with negligible systemic toxicity. Thus, this study provides a useful conditional platform for the precise delivery of DNAzymes and a novel strategy for activatable NO gas-enhanced mitochondrial gene-photodynamic therapy.

Preoperative supplementation of calcitriol and calcium relieves symptom and extent of hypocalcemia in patients undergoing total thyroidectomy and bilateral central compartment neck dissection: A prospective, randomized, open-label, parallel-controlled clinical study.

Background: Hypocalcemia is the most common complication that challenges surgeons performing total thyroidectomy. Conventional postoperative calcium and calcitriol supplement has been reportedly effective; however, a time lag has been reported before taking effect. Therefore, the role of preoperative strategy is yet to be determined. Study design: In this prospective, randomized, open-label, parallel-controlled phase II clinical study (registration number: ChiCTR2200059815), a short-term preoperative administration of calcitriol and calcium was proposed in 210 patients undergoing total thyroidectomy and bilateral central compartment neck dissection. Patients were recruited and randomized (1:1:1) into three groups: (A) combined (preoperative calcitriol and calcium), (B) calcium only (preoperative calcium only), and (C) control (no preoperative intervention). Finally, a total of 172 patients were qualified for final analysis. Results: Our data showed that 16 of 63 patients (25.4%) in the combined group had symptomatic hypocalcemia, whereas more patients from the control group (25 of 57 patients, 43.9%, P = 0.033) had symptomatic hypocalcemia. Further, the postoperative calcium level in the combined group is higher than in the control group (2.15 ± 0.15 vs. 2.09 ± 0.15 mmol/L, P = 0.031). Moreover, patients from the combined group showed lower calcium rates of <2.00 mmol/L (12.7% vs. 28.1%, P = 0.036). Remarkably, compared with the control group, patients with transient hypoparathyroidism in the combined group showed fewer rates for both symptomatic and biochemical hypocalcemia (28.6% vs. 61.1% for symptomatic hypocalcemia; 47.6% vs. 75% for biochemical hypocalcemia). Patients without transient hypoparathyroidism in all three groups showed no significant difference in rates for either symptomatic or biochemical hypocalcemia, indicating that this preoperative strategy is only effective for patients with transient hypoparathyroidism. We did not observe such beneficial effects in patients from the calcium group. Conclusions: Preoperative administration of calcitriol and calcium could reduce symptomatic and biochemical hypocalcemia, especially for those with transient hypoparathyroidism. Moreover, this maneuver could be recommended as a clinical routine in patients undergoing total thyroidectomy and bilateral central compartment neck dissection. Clinical Trial Registration: http://www.chictr.org.cn/edit.aspx?pid=164316&htm=4, identifier ChiCTR2200059815.

Facile preparation of a novel modified biochar-based supramolecular self-assembled g-C3N4 for enhanced visible light photocatalytic degradation of phenanthrene.

The rational design of a novel and environmentally friendly photocatalytic composite for persistent pollutant removal, energy production and catalytic applications have attracted widespread interest. In this study, the new composite composed of KOH-modified biochar and g-C3N4 with different morphologies was successfully prepared with facile supramolecular self-assembly and thermal poly-condensation method. The characterization results of the as-prepared composites suggested that KOH-modified biochar had been well combined with g-C3N4 with different morphologies. These synthesized catalysts were used to degrade phenanthrene under visible light radiation. A-BC/g-C3N4-D performed best and removed 76.72% phenanthrene. Its first-order reaction rate constant was 0.355 h-1, which was 3.7 times higher than that of g-C3N4. A-BC/g-C3N4-D still exhibited a high photocatalytic activity after four cycles. Radical quenching results showed that superoxide radical (·O2-), hydroxyl radical (·OH) and hole (h+) could be used as active species in the redox reaction with phenanthrene. Based on the exploration results of gas chromatography-mass spectrometer (GC-MS), a possible reaction pathway of phenanthrene degradation was also proposed. This study provides a novel strategy for fabricating various high-performance photocatalysts and the removal of persistent organic pollutants.

5-Aminosalicylic acid for treatment of irritable bowel syndrome: A protocol for a systematic review and meta-analysis.

BACKGROUND: The global prevalence of irritable bowel syndrome (IBS) is estimated to be as high as 15%, and it is estimated that IBS has a prevalence of approximately 10% to 20% in Western countries. Some trials showed mesalazine (5-aminosalicylic acid [5-ASA]) might be effective for IBS, but the results still need to be confirmed. Hence, this meta-analysis is designed to assess the efficacy and safety of mesalazine for IBS in adults and children. METHODS: We conducted a comprehensive database search for randomized trials of mesalazine for IBS in PubMed, EMBASE, and the Cochrane Library. The search strategy was performed from inception to December 31, 2019, without restrictions on publication status and language. The reference lists of the included articles were also checked to identify additional studies for potential inclusion. Two reviewers will independently review all literature for inclusion and assess their risk of bias. Two reviewers will independently extract data from eligible studies based on a pre-designed standardized form. Any disagreements will be resolved by consensus. Stata SE 15.0 software will be used for data synthesis. RESULTS: This is the first meta-analysis focusing on mesalazine for the treatment of IBS. We predict it will provide high-quality synthesis on existing evidence for IBS and a relatively comprehensive reference for clinical practice and development of clinical guidelines for IBS. CONCLUSION: This protocol outlined the significance and methodological details of a systematic review of mesalazine for IBS. This ongoing meta-analysis will provide high-quality synthesis on existing evidence for IBS. REGISTRATION: The meta-analysis has been prospectively registered in PROSPERO (CRD42019147860).

Suppression of NF-κB pathway by crocetin contributes to attenuation of lipopolysaccharide-induced acute lung injury in mice.

Crocetin, a carotenoid compound, has been shown to reduce expression of inflammation and inhibit the production of reactive oxygen species. In the present study, the effect of crocetin on acute lung injury induced by lipopolysaccharide (LPS) was investigated in vivo. In the mouse model, pretreatment with crocetin at dosages of 50 and 100 mg/kg reduced the LPS-induced lung oedema and histological changes, increased LPS-impaired superoxide dismutase (SOD) activity, and decreased lung myeloperoxidase (MPO) activity. Furthermore, treatment with crocetin significantly attenuated LPS-induced mRNA and the protein expressions of interleukin-6 (IL-6), macrophage chemoattractant protein-1 (MCP-1), and tumour necrosis factor-α (TNF-α) in lung tissue. In addition, crocetin at different dosages reduced phospho-IκB expression and NF-κB activity in LPS-induced lung tissue alteration. These results indicate that crocetin can provide protection against LPS-induced acute lung injury in mice.

Analysis of differential BRAF(V600E) mutational status in high aggressive papillary thyroid microcarcinoma.

Papillary thyroid cancers often occur as microcarcinoma. Some papillary thyroid microcarcinoma (PTMC) have been considered to be high aggressive according to advanced disease stages, extrathyroidal extension, and severe cervical lymph node metastasis. Although several factors are thought to predict the occurrence of aggressiveness from PTMCs, the origin of aggressiveness has been rarely studied. To answer this question, the correlation between BRAF(V600E) mutation and high aggressive PTMCs was investigated. The clinicopathological characteristic of totally 64 cases of PTMCs was investigated and the BRAF(V600E) mutational status of them was identified. BRAF(V600E) mutation was exclusively detected in PTMCs (37.5%). The data provided no correlation between the occurrence of BRAF(V600E) mutations and clinicopathological parameters, such as sex, age, and tumor-like lesions combination. The prevalence of BRAF(V600E) mutation of PTMCs with high aggressiveness (advanced disease stages, extrathyroidal extension, and nodal metastasis) was significantly higher (p < 0.05) than that of PTMCs without aggressive behavior. The BRAF(V600E) mutated PTMCs exhibited signs of higher aggressiveness than PTMCs without the mutation. BRAF(V600E) mutation may be a marker of high aggressiveness in PTMCs.