Severe acute respiratory syndrome (SARS) and coronavirus disease-2019 (COVID-19): From causes to preventions in Hong Kong.

Hong Kong has been recently attacked by the coronavirus disease-2019 (COVID-19). In late January 2020, it's shown a steadily increasing trend of confirmed cases. There is a 257 in total infected cases confirmed including 4 deaths until 20th of March 2020. To prevent further outbreak of COVID-19, this article discusses the current understanding of COVID-19 and compares with the outbreak of SARS-CoV-2 in 2003 of Hong Kong from the causes, transmission, symptoms, diagnosis, treatments and preventions to study for an applicable measurement to control COVID-19.

Folic acid-modified celastrol nanoparticles: synthesis, characterization, anticancer activity in 2D and 3D breast cancer models.

Celastrol is used in traditional Chinese medicine for treating cancers. However, its low water solubility and poor tumour selection represent major pitfalls for clinical application. In the present study, gold nanoparticle (AuNP) firstly was conjugated with PVP-co-2-dimethylaminoethyl methacrylate (Polymer) and celastrol then modified by folic acid. The as-prepared folate receptor-targeted celastrol AuNP (FCA) was characterized using attenuated total reflection Fourier transform infrared spectroscopy, UV-Vis spectrometry, transmission electron microscope, and inductively coupled plasma mass spectrometry. The physical properties of FCA were also determined in solubility, drug encapsulation and in vitro drug release. Its anticancer activities were assessed in the 2D and 3D breast cancer models. The results showed that FCA was synthesized successfully with good solubility, high encapsulation efficiency and loading content. FCA showed the optimal cumulative release at pH 5.0 and high cellular uptake and exhibited significant inhibition on breast cancer cells. FCA also induced more significant apoptosis either in 2D and 3D breast cancer model than the celastrol AuNP and celastrol alone. These findings demonstrate that FCA improves water solubility of celastrol and enhances its anticancer activities against breast cancer. FCA might be a potential candidate of anticancer drug for breast cancer in the future if further development.

Curcumin-mediated photodynamic inactivation (PDI) against DH5α contaminated in oysters and cellular toxicological evaluation of PDI-treated oysters.

The objective of this study was to evaluate the bactericidal effect of curcumin (CUR)-mediated photodynamic inactivation (PDI) against Escherichia coli DH5α in vitro and in oysters, then further investigate the edible security of PDI-treated oysters based on cellular toxicological methods. First, DH5α cells were irradiated by a 470 nm LED light source with an energy density of 3.6 J/cm2. Colony forming units (CFU) were counted and the viability of DH5α cells was calculated after treatment with CUR-mediated PDI. Intracellular production of reactive oxygen species (ROS) was studied by measuring the fluorescence of 2, 7-dichlorofluorescein (DCF) using a flow cytometry. Membrane permeability was measured using confocal laser scanning microscopy (CLSM) with propidium iodide (PI) staining. After that, the bactericidal effect of CUR-mediated PDI was evaluated in oysters which were pre-contaminated with DH5α cells. Finally, cellular toxicology of PDI-treated oysters was evaluated through morphological observation, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, DNA ladder assay, and nuclear staining. Results showed that the viability of DH5α was significantly decreased in a CUR concentration-dependent manner and resulted in an approximately 3.5-log reduction at the concentration of 20 µM. After treatment with CUR-mediated PDI (20 µM, 3.6 J/cm2), the ROS level in DH5α cells and the membrane permeability markedly increased. Our data demonstrated that CUR-mediated PDI had a good decontamination effect against DH5α contaminated in oysters. After incubation with PDI-treated oysters, fibroblasts L929 cell morphology, MTT absorbance and cell apoptosis had no obvious changes. Our findings preliminarily demonstrated that CUR-mediated PDI-treated oysters had no cytotoxicity to fibroblasts.

Design of an Amphiphilic iRGD Peptide and Self-Assembling Nanovesicles for Improving Tumor Accumulation and Penetration and the Photodynamic Efficacy of the Photosensitizer.

Photodynamic therapy (PDT) is a minimally invasive treatment for many diseases, including infections and tumors. Nevertheless, clinical utilization of PDT is severely restricted due to the shortcomings of the photosensitizers, especially their low water solubility and poor tumor selectivity. iRGD (internalizing RGD, CRGDKGPDC), a nine-unit cyclic peptide, was applied as an active ligand to realize tumor homing and tissue penetration. Herein, we innovatively fabricated a novel OFF-ON mode iRGD-based peptide amphiphile (PA) to self-assemble into spherical nanovesicles to enhance the tumor-targeting and tumor-penetrating efficacy of PDT. To introduce the self-assembling feature into iRGD, a hydrophilic arginine-rich sequence and hydrophobic alkyl chains were sequentially linked to the iRGD motif. A short proline sequence was selected to control the morphology of the self-assembled aggregates. Next, the photosensitizer hypocrellin B (HB) was encapsulated into PA vesicles with a high loading efficiency. The aggregation-caused quenching effect inactivated HB in the PA vesicles; however, the iRGD-peptide-based material was able to be selectively degraded in tumor cells. Thus, the HB fluorescence was recovered to achieve tumor-targeted imaging. This approach endows HB-loaded PA vesicles (HB-PA) with tumor-targeted activation, preferable tumor accumulation, and deep tumor penetration, thus leading to an excellent fluorescence-imaging-guided photodynamic efficacy both in vitro and in vivo. These amphiphilic iRGD aggregates provide a novel strategy for improving the accumulation, penetration, and imaging-guided photodynamic efficacy of photosensitizers.

A Review of Resveratrol as a Potent Chemoprotective and Synergistic Agent in Cancer Chemotherapy.

Background: Cancer has become a major disease endangering human health around the world. Conventional chemotherapy suffers from many side effects including pain, cardiotoxicity, hepatotoxicity, and renal toxicity. This review aims to describe a natural product of resveratrol as a chemoprotective and synergistic agent in the modulation of cancer chemotherapy. Methods: The publications were identified by comprehensive searching of SciFinder, PubMed, Web of Science, and our own reference library. Search terms included combinations of "resveratrol," "cancer," "natural products," "chemotherapy," and "side effects." Selection of material focused on resveratrol reducing the side effects on cancer chemotherapy. Results: Thirty one references were referred in this review to outline resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy, including 22 papers for describing the chemoprotective effects, and 9 papers for illustrating the synergistic effects. Conclusion: This study provides a systematic summary of resveratrol serving as a potent chemoprotective and synergistic agent to reduce the associated-side effects and enhance the therapeutic outcomes in cancer chemotherapy. Further studies in terms of resveratrol on a large amount of preclinical tests and clinical trials are highly demanded.

Sonodynamic action of hypocrellin B triggers cell apoptoisis of breast cancer cells involving caspase pathway.

OBJECTIVES: The aim of the present study is to investigate the effects of sonodynamic action of hypocrellin B on human breast cancer cells and further explore its underlying mechanisms. METHODS: The cell viability of breast cancer MDA-MB-231 cells was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Alterations on cell apoptosis, intracellular reactive oxygen species generation (ROS), mitochondrial membrane potential, and DNA fragmentation was analyzed by flow cytometer. The subcellular localization of hypocrellin B was assessed by a confocal laser scanning microscope. Mitochondria damage and nuclear morphological changes were observed under a fluorescence microscope. To further explore whether caspase pathway was involved in cell apoptotic induction of sonodynamic action of hypocrellin B, the pan-caspase inhibitor Z-Val-Ala-DL-Asp (ome)-Fluoromethylketone (z-VAD-fmk) was added to the cells one hour prior to loading the sonosensitizer, and then cell viability and apoptosis were analyzed after hypocrellin B treatment. RESULTS: Sonodynamic treatment of hypocrellin B HB significantly suppressed cell viability of MDA-MB-231 cells. Sonodynamic action of hypocrellin B caused excessive ROS accumulation, mitochondrial dysfunction, cell apoptosis, DNA fragmentation and nuclear morphological damage. Moreover, the cytotoxicity and cell apoptosis induced by sonodynamic action of hypocrellin B were remarkably rescued by the caspase spectrum inhibitor z-VAD-fmk. CONCLUSIONS: These results demonstrated that hypocrellin B had significant sonodynamic killing and apoptotic induction effect on breast cancer cells. And cell apoptosis induced by sonodynamic action of hypocrellin B was partly dependent on caspase pathway.

Preparation of hypocrellin B nanocages in self-assembled apoferritin for enhanced intracellular uptake and photodynamic activity.

Photodynamic therapy (PDT) is a promising modality, which uses light energy to activate a nontoxic photosensitizer to treat various diseases like cancer and infectious diseases. Hypocrellin B (HB) is a naturally occurring photosensitizer isolated from traditional Chinese medicine Hypocrella bambusea. However, the high hydrophobicity and poor selectivity severely limit its application. Apoferritin, a macromolecular protein, can serve as an attractive nanocage to carry HB while improving its water solubility and tumor selectivity. In this study, novel HB-apoferritin nanoparticles (HB-AFT NPs) were successfully developed by assembling HB within the apoferritin nanocage. The self-assembled HB-AFT NPs have a narrow size distribution and smooth surface with an average diameter of 12 nm and a HB encapsulation efficiency of 85%. The morphological observation and circular dichroism analysis showed that the encapsulation strategy of HB did not impair apoferritin structure, and thus it potentially maintained the tumor targeting ability of apoferritin. Compared with free HB solution, HB-AFT NPs exhibited more pronounced photodynamic activity on MDA-MB-231 cells due to the higher intracellular uptake, increased reactive oxygen species (ROS) production and excellent tumor-targeting. All these results suggest that the self-assembled HB-AFT NPs can be considered as a potential photosensitive drug for tumor targeting photodynamic therapy.

Palmatine hydrochloride mediated photodynamic inactivation of breast cancer MCF-7 cells: Effectiveness and mechanism of action.

Breast cancer is one of the commonest malignant tumors threatening to women. The present study aims to investigate the effect of photodynamic action of palmatine hydrochloride (PaH), a naturally occurring photosensitizer isolated from traditional Chinese medicine (TCM), on apoptosis of breast cancer cells. Firstly, cellular uptake of PaH in MCF-7 cells was measured and the cytotoxicity of PaH itself on breast cancer MCF-7 cells was estimated using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Subcellular localization of PaH in MCF-7 cells was observed using confocal laser scanning microscopy (CLSM). For photodynamic treatment, MCF-7 cells were incubated with PaH and then irradiated by visible light (470nm) from a LED light source. Photocytotoxicity was investigated 24h after photodynamic treatment using MTT assay. Cell apoptosis was analyzed 18h after photodynamic treatment using flow cytometry with Annexin V/PI staining. Nuclear was stained using Hoechst 33342 and observed under a fluorescence microscope. Intracellular production of reactive oxygen species (ROS) was studied by measuring the fluorescence of 2, 7-dichlorofluorescein (DCF) using a flow cytometry. Results showed that PaH treatment alone had no or minimum cytotoxicity to MCF-7 cells after incubation for 24h in the dark. After incubation for 40min, the cellular uptake of PaH reached to the maximum, and PaH mainly located in mitochondria and endoplasmic reticulum of MCF-7 cells. Photodynamic treatment of PaH demonstrated a significant photocytotoxicity on MCF-7 cells, induced remarkable cell apoptosis and significantly increased intracellular ROS level. Our findings demonstrated that PaH as a naturally occurring photosensitizer induced cell apoptosis and significantly killed MCF-7 cells.

Photodynamic action of palmatine hydrochloride on colon adenocarcinoma HT-29 cells.

Palmatine hydrochloride (PaH) is a natural active compound from a traditional Chinese medicine (TCM). The present study aims to evaluate the effect of PaH as a new photosensitizer on colon adenocarcinoma HT-29 cells upon light irradiation. Firstly, the absorption and fluorescence spectra of PaH were measured using a UV-vis spectrophotometer and RF-1500PC spectrophotometer, respectively. Singlet oxygen ((1)O2) production of PaH was determined using 1, 3-diphenylisobenzofuran (DPBF). Dark toxicity of PaH was estimated using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cellular uptake of PaH in HT-29 cells was detected at different time intervals. Subellular localization of PaH in HT-29 cells was observed using confocal laser fluorescence microscopy. For photodynamic treatment, HT-29 cells were incubated with PaH and then irradiated by visible light (470nm) from a LED light source. Photocytotoxicity was investigated 24h after photodynamic treatment using MTT assay. Cell apoptosis was observed 18h after photodynamic treatment using a flow cytometry with Annexin V/PI staining. Results showed that PaH has an absorption peak in the visible region from 400nm to 500nm and a fluorescence emission peak at 406nm with an excitation wavelength of 365nm. PaH was activated by the 470nm visible light from a LED light source to produce (1)O2. Dark toxicity showed that PaH alone treatment had no cytotoxicity to HT-29 cancer cells and NIH-3T3 normal cells after incubation for 24h. After incubation for 40min, the cellular uptake of PaH reached to the maximum and PaH was located in mitochondria. Photodynamic treatment of PaH demonstrated a significant photocytotoxicity on HT-29 cells. The rate of cell death increased significantly in a PaH concentration-dependent and light dose-dependent manner. Further evaluation revealed that the early and late apoptotic rate of HT-29 cells increased remarkably up to 21.54% and 5.39% after photodynamic treatment of PaH at the concentration of 5µM and energy density of 10.8J/cm(2). Our findings demonstrated that PaH as a naturally occurring photosensitizer has potential in photodynamic therapy on colon adenocarcinoma.

Photodynamic effect of curcumin on Vibrio parahaemolyticus.

Vibrio parahaemolyticus (V. parahaemolyticus) is currently a major cause of bacterial diarrhoea associated with seafood consumption. The objective of this study was to determine the inactivation effect of curcumin-mediated photodynamic action on V. parahaemolyticus. First of all, V. parahaemolyticus suspended in PBS buffer was irradiated by a visible light from a LED light source with an energy density of 3.6J/cm(2). Colony forming units (CFU) were counted and the viability of V. parahaemolyticus cells was calculated after treatment. Singlet oxygen ((1)O2) production after photodynamic action of curcumin was evaluated using 9,10-Anthracenediyl-bis (methylene) dimalonic acid (ADMA). Bacterial outer membrane protein was extracted and analyzed using electrophoresis SDS-PAGE. DNA and RNA of V. parahaemolyticus were also extracted and analyzed using agarose gel electrophoresis after photodynamic treatment. Finally, the efficacy of photodynamic action of curcumin was preliminarily evaluated in the decontamination of V. parahaemolyticus in oyster. Results showed that the viability of V. parahaemolyticus was significantly decreased to non-detectable levels over 6.5-log reductions with the curcumin concentration of 10 and 20µM. Photodynamic action of curcumin significantly increased the singlet oxygen level with the curcumin concentration of 10µM. Notable damage was found to bacterial outer membrane proteins and genetic materials after photodynamic treatment. Photodynamic action of curcumin reduced the number of V. parahaemolyticus contaminating in oyster to non-detectable level. Our findings demonstrated that photodynamic action of curcumin could be a potentially good method to inactivate Vibrio parahaemolyticus contaminating in oyster.

The antibacterial effect of sinoporphyrin sodium photodynamic therapy on Staphylococcus aureus planktonic and biofilm cultures.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus (S. aureus) are important causes of nosocomial and medical-device-related infections. Photodynamic treatment (PDT) has been proposed as an alternative approach for the inactivation of bacteria. Sinoporphyrin sodium (DVDMS) is a newly identified photosensitizer and has high photo-sensitivity when used in PDT. This study aims to evaluate the antibacterial effect of DVDMS mediated PDT on S. aureus planktonic and biofilm cultures. STUDY DESIGN/MATERIALS AND METHODS: The uptake of DVDMS in S. aureus was evaluated according to photometry after alkali lysis. Then bacteria were incubated with DVDMS and exposed to light treatment. After PDT treatment, counting colony-forming units (CFU) was applied to estimate the bactericidal effect. Intracellular reactive oxygen species (ROS) production was detected by flow cytometry. Scanning electron microscope (SEM) was performed to assess the disruption of biofilm. RESULTS: With the incubation time increased, the relative fluorescence intensity of DVDMS in bacteria increased and reached peak at 75 minutes. DVDMS alone did not produce significant toxicity compared with the untreated group, while, remarkable survival decrease was observed in PDT groups in a dose-dependent manner. More than 90% of the bacteria were effectively killed by the combined treatment of 2 µM DVDMS with 10 J/cm2 light irradiation, and 4-log reduction in CFU was observed after 5 µM DVDMS treatment followed by 100 J/cm2 light irradiation. Intracellular ROS level was significantly enhanced after PDT treatment. The disruption of biofilm was confirmed by SEM, suggesting DVDMS-PDT effectively damaged the biofilm. CONCLUSION: These results indicate DVDMS-PDT presents significant bactericidal activity.

Sonodynamic action of chlorin e6 on Staphylococcus aureus and Escherichia coli.

Bacteria remain a great threat to human health. In the present study, we examined whether sonodynamic action of chlorin e6 had antibacterial activity on gram-positive bacterial strain Staphylococcus aureus (S. aureus) and gram-negative bacterial strain Escherichia coli (E. coli). Colony forming unit (CFU) assay showed that sonodynamic treatment of chlorin e6 induced a 2-log reduction in CFU of E. coli cells, 7-log reduction in CFU of S. aureus. Fluorescent microscopy observed that dead cells remarkably increased whereas live cells decreased after sonodynamic treatment of chlorin e6 on S. aureus cells. We first demonstrated that sonodynamic action of chlorin e6 has antibacterial effect on both gram-positive and negative bacteria, more powerful on gram-positive bacteria.