Inhibitory Effects and Related Molecular Mechanisms of Huanglian-Ganjiang Combination Against H1N1 Influenza Virus.

Influenza is an infectious acute respiratory disease with complications and a high mortality rate; the effective medicines for influenza therapy are limited. "Huanglian" or Coptidis Rhizoma, Coptis chinensis Franch., Ranunculaceae, and "ganjiang" or Zingiberis Rhizoma, Zingiber officinale Roscoe, Zingiberaceae, combination is clinically used for treating respiratory diseases. HPLC was applied for the quantification of berberine hydrochloride (1.101 mg/ml) and 6-gingerol (38.41 µg/ml) in the H2O-soluble extract of the herbal formulation. In this study, the effect of "huanglian"- "ganjiang" extract on influenza virus H1N1-induced acute pulmonary inflammation was evaluated, in addition to the investigation of its anti-influenza mechanism in a mouse model. The analyzed herbal combination inhibited the expression of cytokine IL-6 and stimulated the expression of IL-2 in the serum of influenza virus-infected mice. Meanwhile, the herbal combination downregulated the gene and protein expression levels of TLR3, TLR7, MyD88, RIG-I, MAVS, TRAF3, and NF-κB p65, which are key targets of toll-like and RIG-I-like receptor signaling pathways in mice. In addition, the herbal combination could also promote the combination of intracellular autophagosomes and lysosomes in autophagosome-lysosome formation and improve impaired fusion of autophagosomes and lysosomes by influenza virus. This study suggested that the "huanglian"- "ganjiang" extract may be a candidate therapeutic strategy for the treatment of H1N1 influenza. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-023-00372-z.

Design, synthesis, and evaluation of antitumor activity of novel C-6 sulfhydryl-substituted and 20-substituted derivatives of celastrol.

Celastrol has been identified as a potential candidate for anticancer drug development. In this study, 28 novel celastrol derivatives with C-6 sulfhydryl substitution and 20-substitution were designed and synthesized, and their antiproliferative activity against human cancer cells and non-malignant human cells was evaluated, with cisplatin and celastrol being used as controls. The results showed that most of the derivatives had enhanced in vitro anticancer activity compared to the parent compound celastrol. Specifically, derivative 2f demonstrated the most potent inhibitory potential and selectivity against HOS with an IC50 value of 0.82 µM. Our study provides new insights into the structure-activity relationship of celastrol and suggests that compound 2f may be a promising drug candidate for the treatment of osteosarcoma.

Pharmacokinetics and Pharmacodynamics of Huanglian-Houpo Decoction Based on Berberine Hydrochloride and Magnolol Against H1N1 Influenza Virus.

BACKGROUND AND OBJECTIVES: Huanglian-Houpo decoction (HH), which is recorded in the famous traditional Chinese medicine monograph "Puji Fang," contains two individual herbs, Huanglian (Rhizoma coptidis) and Houpo (Magnoliae officinalis cortex). It was regularly used to treat seasonal epidemic colds and influenzas in ancient China. Our laboratory discovered that HH has a significant anti-H1N1 influenza virus effect. However, no pharmacokinetic and pharmacodynamic data concerning the anti-H1N1 influenza virus activity of HH are available to date. In the current study, the concentration-time profiles of two major components of HH, berberine and magnolol, in rat plasma were investigated. METHODS: An integrate pharmacokinetic approach was developed for evaluating the holistic pharmacokinetic characteristics of berberine and magnolol from HH. Additionally, the inhibition rate and levels of IFN-ß in MDCK cells infected by influenza virus were analyzed. Data were calculated using 3p97 with pharmacokinetic analysis. RESULTS: The estimated pharmacokinetic parameters were maximum plasma concentration (Cmax) 0.9086 µg/ml, area under the concentration-time curve (AUC) 347.74 µg·min/ml, and time to reach Cmax (Tmax) 64.69 min for berberine and Cmax = 0.9843 µg/ml, AUC= 450.64 µg·min/ml, Tmax = 56.86 min for magnolol, respectively. Furthermore, integrated pharmacokinetic and pharmacodynamic analysis showed that the highest plasma concentration, inhibition rate and interferon-ß (IFN-ß) secretion of HH first increased and then weakened over time, reaching their peaks at 60 min. The plasma concentration of HH is directly related to the anti-influenza virus effect. CONCLUSION: The results indicated that berberine and magnolol are the main active ingredients of HH related to its anti-influenza virus effect, which is related to the improvement of IFN-ß secretion.

Inhibitory effects and related molecular mechanisms of total flavonoids in Mosla chinensis Maxim against H1N1 influenza virus.

OBJECTIVE: The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice. METHODS: The viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF. The concentrations of inflammatory cytokines and anti-oxidant factors were detected by ELISA. RT-PCR and western blot assays were used to determine the expression level of TLR pathway's key genes and proteins in lung tissues. RESULTS: We found that the pathological changes of lung in the viral pneumonia mice obviously alleviated by STF treatments and the STF (288 or 576 mg/kg) could significantly decrease lung indices. Moreover, the up-regulation (IL-6, TNF-α, IFN-γ, and NO) and down-regulation (IL-2, SOD and GSH) of inflammatory cytokines and anti-oxidant factors were associated with higher clearance of virus and reduction of inflammatory lung tissue damage. Meanwhile, the expression levels of TLR3, TLR7, MyD88, TRAF3 and NF-κB p65 of the TLR pathway were reduced by STF treatment. CONCLUSIONS: This study suggested that STF may be a promising candidate for treating H1N1 influenza and subsequent viral pneumonia.

A Molecular Combination of Zinc(II) Phthalocyanine and Tamoxifen Derivative for Dual Targeting Photodynamic Therapy and Hormone Therapy.

The combination of photodynamic therapy and other cancer treatment modalities is a promising strategy to enhance therapeutic efficacy and reduce side effects. In this study, a tamoxifen-zinc(II) phthalocyanine conjugate linked by a triethylene glycol chain has been synthesized and characterized. Having tamoxifen as the targeting moiety, the conjugate shows high specific affinity to MCF-7 breast cancer cells overexpressed estrogen receptors (ERs) and tumor tissues, therefore leading to a cytotoxic effect in the dark due to the cytostatic tamoxifen moiety, and a high photocytotoxicity due to the photosensitizing phthalocyanine unit against the MCF-7 cancer cells. The high photodynamic activity of the conjugate can be attributed to its high cellular uptake and efficiency in generating intracellular reactive oxygen species. Upon addition of exogenous 17ß-estradiol as an ER inhibitor, the cellular uptake and photocytotoxicity of the conjugate are reduced significantly. As shown by confocal microscopy, the conjugate is preferentially localized in the lysosomes of the MCF-7 cells.

Anti-H1N1 influenza effects and its possible mechanism of Huanglian Xiangru Decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangliang Xiangru Decoction (HXD), which is described in a famous TCM monograph "Book of Nanyang for Life Savin", is frequently used for treating cold in summer and summer heat-dampness. AIM OF THE STUDY: To date, no pharmacological study on the anti-H1N1 influenza properties of HXD has been reported. The aim of the present study was to evaluate the therapeutic action of HXD on HIN1-induced acute pulmonary inflammation and its anti-influenza mechanism focus to TLRs signal pathway in a mouse model. MATERIALS AND METHODS: the mice were intranasally infected with influenza virus to induce viral pneumonia, and then treated with different doses of HXD. The Lung index and pathological changes in the lung tissue of mice were investigated to value the anti-influenza virus effect of HXD. The concentrations of cytokines (IL-2, IL-6, TNF-α and IFN-γ) and anti-oxidant factor (NO, SOD and GSH) in serum of mice were determined with ELISA. RT-PCR and Western blot were used to determine the mRNA and protein expression of TLR3, TLR7, MyD88,TRAF3 and NF-κB p65 in the lung tissues, which are the key targets of TLRs pathway. RESULTS: Compared with the infection group, the lung index of mice in ribavirin group, HXD high dose group and HXD middle dose group were significantly decreased, the lung indexes of these groups were 10.36±1.14mg/g, 9.89±0.79mg/g, and 10.97±0.67mg/g. Moreover, pathological changes were remarkable alleviated. HXD can reduce the contents of IL-6, TNF-α and IFN-γ, NO, and increase the contents of IL-2, SOD, GSH in serum of infected-mice significantly. At the same time, HXD can reduce the mRNA and protein expression of TLR3, TLR7, MyD88,TRAF3 and NF-κB p65 in the lung tissues of infected-mice significantly. CONCLUSIONS: HXD has significant effects on H1N1 influenza by a quantity-effect relationship, and plays its anti-influenza effect by enhancing the body's antioxidant capacity, regulating the body's immune function and the host's TLRs pathway.

Molecular-target-based anticancer photosensitizer: synthesis and in vitro photodynamic activity of erlotinib-zinc(II) phthalocyanine conjugates.

Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib-zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conjugates can successfully target EGFR-overexpressing cancer cells owing to the presence of the small molecular-target-based anticancer agent erlotinib. All conjugates were found to be essentially non-cytotoxic in the absence of light (up to 50 µM), but upon illumination, they show significantly high photo-cytotoxicity toward HepG2 cells, with IC50 values as low as 9.61-91.77 nM under a rather low light dose (λ=670 nm, 1.5 J cm(-2) ). Structure-activity relationships for these conjugates were assessed by determining their photophysical/photochemical properties, cellular uptake, and in vitro photodynamic activities. The results show that these conjugates are highly promising antitumor agents for molecular-target-based photodynamic therapy.

Synthesis and in vitro anticancer activity of zinc(II) phthalocyanines conjugated with coumarin derivatives for dual photodynamic and chemotherapy.

The combination of photodynamic therapy and chemotherapy is a promising strategy to overcome growing problems in contemporary medicine, such as low therapeutic efficacy and drug resistance. Four zinc(II) phthalocyanine-coumarin conjugates were synthesized and characterized. In these complexes, zinc(II) phthalocyanine was used as the photosensitizing unit, and a coumarin derivative was selected as the cytostatic moiety; the two components were linked via a tri(ethylene glycol) chain. These conjugates exhibit high photocytotoxicity against HepG2 human hepatocarcinoma cells, with low IC50 values in the range of 0.014-0.044 µM. The high photodynamic activities of these conjugates are in accordance with their low aggregation tendency and high cellular uptake. One of these conjugates exhibits high photocytotoxicity and significantly higher chemocytotoxicity. The results clearly show that the two antitumor components in these conjugates work in a cooperative fashion. As shown by confocal microscopy, the conjugates can localize in the mitochondria and lysosomes, and one of the conjugates can also localize in the cell nuclei.

[SERS spectrum recognition for Malachite Green real-time detection in aquaculture used seawater].

Surface enhanced Raman spectroscopy (SERS) is a useful chemical analysis technique for its high sensitivity, which was used for Malachite Green qualitative analysis in real cases in the present article. Automatic recognition algorithms were put forward, which is a combination of three modules, including a robust Fourier transform for background rejection, a principal component analysis based character extraction method and artificial neural networks for classifying. Low-frequency background was rejected by iterative Fourier transform in order to eliminate the effect of variable background. The best principal component combination was obtained according to the Euclidean distances between-class and within-class in the sample space. And a three-layer back-propagating neural network was constructed for classifying. As it was shown, it would both minimize the network and reduce the classifying mistakes from variable baseline and Raman characters of other substances in seawater with best principal component combination. Malachite Green real-time detection in aquaculture used seawater was realized with a lower density limit of 0. 1 microg L-1. Moreover, the method proposed in this article could be extended for other sol analysis based on SERS technique.

A novel strategy for targeting photodynamic therapy. Molecular combo of photodynamic agent zinc(II) phthalocyanine and small molecule target-based anticancer drug erlotinib.

In this study, two phthalocyanine-erlotinib conjugates linked by an oligoethylene glycol chain have been synthesised and fully characterised. Having erlotinib as the targeting moiety, the two conjugates exhibited high specific affinity to HepG2 cancer cells and tumour tissues, therefore leading to high photodynamic activity.

Correlations between quality indexes of chest compression.

BACKGROUND: Cardiopulmonary resuscitation (CPR) is a kind of emergency treatment for cardiopulmonary arrest, and chest compression is the most important and necessary part of CPR. The American Heart Association published the new Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care in 2010 and demanded for better performance of chest compression practice, especially in compression depth and rate. The current study was to explore the relationship of quality indexes of chest compression and to identify the key points in chest compression training and practice. METHODS: Totally 219 healthcare workers accepted chest compression training by using Laerdal ACLS advanced life support resuscitation model. The quality indexes of chest compression, including compression hands placement, compression rate, compression depth, and chest wall recoil as well as self-reported fatigue time were monitored by the Laerdal Computer Skills and Reporting System. RESULTS: The quality of chest compression was related to the gender of the compressor. The indexes in males, including self-reported fatigue time, the accuracy of compression depth and the compression rate, the accuracy of compression rate, were higher than those in females. However, the accuracy of chest recoil was higher in females than in males. The quality indexes of chest compression were correlated with each other. The self-reported fatigue time was related to all the indexes except the compression rate. CONCLUSION: It is necessary to offer CPR training courses regularly. In clinical practice, it might be better to change the practitioner before fatigue, especially for females or weak practitioners. In training projects, more attention should be paid to the control of compression rate, in order to delay the fatigue, guarantee enough compression depth and improve the quality of chest compression.

[Effects of auditory integrative training on autistic children].

OBJECTIVE: To explore the short-term treatment effect of the auditory integrative training on autistic children and provide them with clinical support for rehabilitative treatment. METHODS: A total of 81 cases of autistic children were selected through the standard of DSM-4 and clinical case study was used. They were divided randomly into experimental group and control one, and respectively received auditory integrative training and no training based on the multiple therapies. The patients were investigated using clinical manifestation and Autism Behavior Checklist (ABC) and intelligence quotient (IQ) before and after six months of treatment. The effect was evaluated through the changes of clinical manifestations and scores of ABC and IQ. The changes of scores of IQ were determined with Gesell and WPPSI or WISC-R. RESULTS: Compared with 40 patients of the control group after the six months of the auditory integrative training, 41 of the experimental group had greatly improved in many aspects, such as the disorders of their language, social interactions and typical behavior symptoms while they had not changed in their abnormal behaviors. The scores of IQ or DQ had increased and scores of ABC had dropped. The differences between the two groups were greatly significant in statistics (P < 0.01). The decreasing level of both ABC scores and the increasing level of the IQ scores were negatively correlated with age, and the decreasing level of ABC scores was in line regression(positive correlation) with base IQ. CONCLUSION: The treatment of auditory integrative training (AIT) could greatly improve on language disorders, the difficulties of social interactions, typical behavior symptoms and developmental levels,therefore it is positive to the autistic children in its short-term treatment effect.

Therapeutic effects of modified Danggui Sini Decoction on plasma level of advanced glycation end products in patients with Wagner grade 0 diabetic foot: a randomized controlled trial.

BACKGROUND: Many studies have demonstrated association between advanced glycation end products (AGEs) and diabetic angiopathy. There are certain advantages of traditional Chinese medicine (TCM) therapy in treatment of these diseases. OBJECTIVE: To evaluate the therapeutic effects and safety of modified Danggui Sini Decoction, a compound traditional Chinese herbal medicine for nourishing blood to warm meridians, on plasma level of AGEs in patients with Wagner grade 0 diabetic foot ulcers of blood stasis or/and kidney yang deficiency syndrome. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A random and positive control method was adopted. Seventy-two cases of Wagner classification of grade 0 diabetic foot ulcers with blood stasis or/and kidney yang deficiency syndrome were randomly divided into treatment group and control group. There were thirty-six cases in each group. All the patients were collected from Maoming Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine. Patients received oral and written information about the clinical procedures before giving their written informed consent. The study was approved by the Ethics Committee of Maoming Hospital of Traditional Chinese Medicine. The patients in the treatment group were treated with modified Danggui Sini Decoction, and the patients in the control group were treated with cilostazol. A course of treatment was 14 days, and the patients in the two groups were treated for 3 courses. MAIN OUTCOME MEASURES: The changes of clinical symptoms, ankle-brachial index (ABI), electromyography, lower extremity arteries measured by ultrasonic Doppler, fasting blood glucose, hemoglobin A1c, fibrinogen, and plasma level of AGEs were detected in the two groups before and after treatment. The safety of modified Danggui Sini Decoction was assessed by laboratory data and adverse events. RESULTS: There were statistical differences in clinical efficacy, ABI, lower extremity arteries hemodynamics, and nerve conduction velocity between the two groups (P<0.05, P<0.01). The plasma level of AGEs after treatment was significantly decreased in the two groups, and the level of AGEs in the treatment group was lower than that in the control group (P<0.05). CONCLUSION: Modified Danggui Sini Decoction can improve clinical symptoms in patients with diabetic foot ulcers of Wagner grade 0 and it shows therapeutic effects on diabetes complicated with vascular diseases.