Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Bleeding the Excited State Energy to the Utmost: Single-Molecule Iridium Complexes for In Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low-Power Laser.

A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrate high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato-/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808 nm laser irradiation by dual photodynamic therapy and photothermal therapy and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors.

Dinuclear osmium complexes as mitochondrion-targeting antitumor photothermal agents in vivo.

Four dinuclear osmium complexes have been constructed for antitumor phototherapy. The most potent Os4 has extremely high photothermal conversion capability under irradiation of an 808 nm low-power laser, targets mitochondria in human melanoma cells without nucleus affinity, and acts as an antitumor photothermal therapy agent in vitro and in vivo.

Efficacy and safety of Wuling capsule for insomnia disorder: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Wuling capsule has been used in treatment of insomnia disorder in China for decades, but the reported treatment efficacy of different studies was not consistent. This study intended to evaluate the efficacy and safety of Wuling capsule for insomnia disorder, so as to provide evidence for clinical application. METHODS: Eight databases (MEDLINE, EMBASE, Ovid, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, Chinese Biomedical Database and Wanfang) were searched from inception to September 14, 2021. Randomized controlled trials (RCTs) comparing Wuling capsule with controls in adults with insomnia disorder were eligible. The primary outcome was sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI), and the secondary outcomes were severity of insomnia disorder measured by Sleep Dysfunction Rating Scale (SDRS) and adverse events. This study was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. RESULTS: Nineteen RCTs with a total of 1850 participants were included. In terms of sleep quality assessed by PSQI, Wuling capsule significantly lowered PSQI score (MD: -1.92, 95% CI: [-2.34, -1.50], P < 0.00001, I2 = 95%) compared to controls, and the effect of Wuling capsule was significantly better than control no matter when Wuling capsule as monotherapy (MD: -1.71, 95% CI: [-2.33, -1.09], P < 0.00001, I2 = 97%) or as adjunctive therapy (MD: -2.10, 95% CI: [-2.66, -1.55], P < 0.00001, I2 = 90%). Wuling capsule was more effective for the treatment duration lasted 8 weeks (MD: -2.57, 95% CI: [-3.52, -1.62], P < 0.00001, I2 = 93%) than 4 weeks (MD: -1.68, 95% CI: [-2.13, -1.22], P < 0.00001, I2 = 95%). In terms of severity of insomnia disorder measured by SDRS, Wuling capsule significantly reduced SDRS score (MD: -4.21, 95% CI: [-4.95, -3.46], P < 0.00001, I2 = 0%) compared to benzodiazepines. Wuling capsule significantly reduced adverse events compared to controls (RR: 0.47, 95% CI: [0.34, 0.65], P < 0.00001, I2 = 43%). CONCLUSION: Wuling capsule can safely and effectively improve sleep quality in patients with insomnia disorder. However, these findings require careful recommendation due to the high heterogeneity and high risk of bias in the included trials. Clinical trials with higher quality designs are needed.

A review on the structure and pharmacological activity of phenylethanoid glycosides.

Phenylethanoid glycosides (PhGs) are compounds made of phenylethyl alcohol, caffeic acid and glycosyl moieties. The first published references about phenylethanoid glycosides concerned the isolation of echinacoside from Echinaceu ungustifolia (Asteraceae) in 1950 and verbascoside from Verbascum sinuatum (Scrophulariaceae) in 1963. Over the past 60 years, many compounds with these structural characteristics have been isolated from natural sources, and most of these compounds possess significant bioactivities, including antibacterial, antitumor, antiviral, anti-inflammatory, neuro-protective, antioxidant, hepatoprotective, and immunomodulatory activities, among others. In this review, we will summarize the phenylethanoid glycosides described in recent papers and list all the compounds that have been isolated over the past few decades. We will also attempt to present and assess recent studies about the separation, extraction, determination, and pharmacological activity of the excellent natural components, phenylethanoid glycosides.

[Research progress in root rot diseases of Chinese herbal medicine and control strategy by antagonistic microorganisms].

In recent years, root rot diseases of Chinese herbal medicine have been posing grave threat to the development of the traditional Chinese medicine industry. This article presents a review on the occurring situation of the root rot disease, including the occurrence of the disease, the diversity of the pathogens, the regional difference in dominant pathogens,and the complexity of symptoms and a survey of the progress in bio-control of the disease using antagonistic microorganisms. The paper also discusses the existing problems and future prospects in the research.

Epitope mapping and immunological characterization of a major allergen TBa in tartary buckwheat.

Predicted by an antigenic program, full-length tartary buckwheat allergen (TBa) is divided into six fragments: E1, E2, E12, E3, E4 and E34. Immunological assays revealed that E1 has the greatest binding activity to patients' serum IgE. Five mutants of E1 gene (L39R, L42R, L47R, V52R and L54R) were constructed using site-directed mutagenesis and each protein was expressed in Escherichia coli BL21. Following purification by Ni(2+) affinity chromatography, ELISA and dot-blot were performed for wild type E1 and its mutants using sera from buckwheat allergic patients and healthy controls. Mutants L42R, L47R, and L54R had weaker IgE binding activity to patient's sera than wild-type E1 implying that Leu42, Leu47, and Leu54 might be involved in the allergic activity of TBa.

[Expression and immunological characterization of the epitopes in tartary buckwheat allergen].

AIM: To determine the most important region in tartary buckwheat allergen. METHODS: The gene of epitopes was amplified by PCR using the primers designed according to TBa cDNA. Four expression vectors containing the gene of epitopes were constructed, and then transformed into the E.coli BL21(DE3) host cells. The expression products were purified by Ni(2+);-NTA agarose affinity chromatography column and indirect ELISA, inhibition ELISA and Dot blot was performed using sera from allergenic patients. RESULTS: The purified proteins were obtained and the immunological results showed that E1 exhibite stronger IgE binding to patient's serum than the other epitopes. CONCLUSION: E1 is probably the most important region in tartary buckwheat allergen binding to buckwheat allergic sera IgE.

[Effect of genistein on hepatic stellate cell proliferation and lipid peroxidation in vitro].

OBJECTIVE: To investigate the effect of genistein on the proliferation and lipid peroxidation of hepatic stellate cells (HSC) in vitro and its the protective effect against hepatic fibrosis. METHODS: Rat hepatic stellate cells (HSC-T6 cells) were divided into 3 groups and incubated in the presence of 0.1 mol/L hydrogen dioxide followed by washing with PBS for 3 times. Genistein at different concentrations was added into the cell culture meclia, and after 48 h of incubation, the cell proliferation was assessed with MTT assay and the levels of superoxide dismutase (SOD), malonaldehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-PX) in the supernatant of the cell culture were measured. RESULTS: Genistein at different concentrations inhibited the cell proliferation, showing a dose-effect relationship. Genistein significantly decreased the production of intracellular MDA and GSH and increased SOD and GSH PX activity. CONCLUSION: Genistein can prevent the formation of hepatic fibrosis probably by decreasing HSC proliferation and lipid peroxidation.

Mechanisms of monocrotophos resistance in cotton bollworm, Helicoverpa armigera (Hübner).

Insensitive acetylcholinesterase was identified as a resistance mechanism by comparing biochemical analysis with a laboratory selected monocrotophos resistant cotton bollworm (RR: 200) and the susceptible strain. The cDNA encoding AChE was cloned by the method of RACE (rapid amplification of cDNA ends). The complete AChE gene deduced from the cDNA consisted of a putative signal peptide of 32 amino acid residues, a mature protein of 615 residues, 5' untranslated regions (UTR) of 315 bp and 3' UTR of 324 bp. The coding sequence had a high degree of homology to the AChE from other insect species reported in the GenBank. After comparing analysis of the entire AChE gene sequence from 5 resistant and 6 susceptible cotton bollworm individuals, nine mutations were identified. One of them, the Ala/Thr mutation, is likely to be responsible for the AChE insensitivity to monocrotophos.