Comparison of the Differences between Two-Photon Excitation, Upconversion, and Conventional Photodynamic Therapy on Cancers in In Vitro and In Vivo Studies.

Photodynamic therapy (PDT) is a minimally invasive treatment for several diseases. It combines light energy with a photosensitizer (PS) to destroy the targeted cells or tissues. A PS itself is a non-toxic substance, but it becomes toxic to the target cells through the activation of light at a specific wavelength. There are some limitations of PDT, although it has been used in clinical studies for a long time. Two-photon excitation (TPE) and upconversion (UC) for PDT have been recently developed. A TPE nanoparticle-based PS combines the advantages of TPE and nanotechnology that has emerged as an attractive therapeutic agent for near-infrared red (NIR) light-excited PDT, whilst UC is also used for the NIR light-triggered drug release, activation of 'caged' imaging, or therapeutic molecules during PDT process for the diagnosis, imaging, and treatment of cancers. METHODS: Nine electronic databases were searched, including WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), without any language constraints. TPE and UCNP were evaluated to determine if they had different effects from PDT on cancers. All eligible studies were analyzed and summarized in this review. RESULTS: TPE-PDT and UCNP-PDT have a high cell or tissue penetration ability through the excitation of NIR light to activate PS molecules. This is much better than the conventional PDT induced by visible or ultraviolet (UV) light. These studies showed a greater PDT efficacy, which was determined by enhanced generation of reactive oxygen species (ROS) and reduced cell viability, as well as inhibited abnormal cell growth for the treatment of cancers. CONCLUSIONS: Conventional PDT involves Type I and Type II reactions for the generation of ROS in the treatment of cancer cells, but there are some limitations. Recently, TPE-PDT and UCNP-PDT have been developed to overcome these problems with the help of nanotechnology in in vitro and in vivo studies.

Photodynamic Action of Curcumin and Methylene Blue against Bacteria and SARS-CoV-2-A Review.

Coronavirus disease 19 (COVID-19) has occurred for more than four years, and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is a strain of coronavirus, which presents high rates of morbidity around the world. Up to the present date, there are no therapeutics that can avert this form of illness, and photodynamic therapy (PDT) may be an alternative approach against SARS-CoV-2. Curcumin and methylene blue have been approved and used in clinical practices as a photosensitizer in PDT for a long time with their anti-viral properties and for disinfection through photo-inactivated SARS-CoV-2. Previously, curcumin and methylene blue with antibacterial properties have been used against Gram-positive bacteria, Staphylococcus aureus (S. aureus), and Gram-negative bacteria, Escherichia coli (E. coli), Enterococcus faecalis (E. faecalis), and Pseudomonas aeruginosa (P. aeruginosa). METHODS: To conduct a literature review, nine electronic databases were researched, such as WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), without any regard to language constraints. In vitro and in vivo studies were included that evaluated the effect of PDT mediated via curcumin or methylene blue to combat bacteria and SARS-CoV-2. All eligible studies were analyzed and summarized in this review. RESULTS: Curcumin and methylene blue inhibited the replication of SARS-CoV-2. The reactive oxygen species (ROS) are generated during the treatment of PDT with curcumin and methylene blue to prevent the attachment of SARS-CoV-2 on the ACE2 receptor and damage to the nucleic acids either DNA or RNA. It also modulates pro-inflammatory cytokines and attenuates the clotting effects of the host response. CONCLUSION: The photodynamic action of curcumin and methylene blue provides a possible approach against bacteria and SARS-CoV-2 infection because they act as non-toxic photosensitizers in PDT with an antibacterial effect, anti-viral properties, and disinfection functions.

Chinese medicinal herbs as potential prodrugs for obesity.

Obesity is a leading worldwide health threat with ever-growing prevalence, it promotes the incidence of various diseases, particularly cardiovascular disease, metabolic syndrome, diabetes, hypertension, and certain cancers. Traditional Chinese Medicine (TCM) has been used to control body weight and treat obesity for thousands of years, Chinese medicinal herbs provide a rich natural source of effective agents against obesity. However, some problems such as complex active ingredients, poor quality control, and unclear therapeutic mechanisms still need to be investigated and resolved. Prodrugs provide a path forward to overcome TCM deficiencies such as absorption, distribution, metabolism, excretion (ADME) properties, and toxicity. This article aimed to review the possible prodrugs from various medicinal plants that demonstrate beneficial effects on obesity and seek to offer insights on prodrug design as well as a solution to the global obesity issues.

Proteomic analysis reveals that pheophorbide a-mediated photodynamic treatment inhibits prostate cancer growth by hampering GDP-GTP exchange of ras-family proteins.

BACKGROUND: We previously reported that pheophorbide a (PhA), excited by 630 nm light, significantly inhibited the growth of prostate cancer cells. In this study, we employed whole-cell proteomics to investigate photodynamic treatment (PDT)-related proteins. METHODS: Two-dimensional gel electrophoresis (2-DE) coupled with tandem mass spectrometry was employed to reveal the proteins involved in PhA-mediated PDT in LNCaP and PC-3 prostate cancer cells. RESULTS: After PhA-PDT treatment, decreased expression of translationally-controlled tumor protein (TCTP) was found in both PC-3 and LNCaP whole-cell proteomes. In contrast, human rab GDP dissociation inhibitor (GDI) in LNCaP cells and ras-related homologs GDI in PC-3 cells were up-regulated. CONCLUSIONS: GDP-GTP exchange is an underlying target of photodynamic treatment in prostate cancer cells.

Efficacy of abdominal acupuncture for neck pain: A randomized controlled trial.

OBJECTIVE: This study aims to provide evidence regarding the clinical efficacy of abdominal acupuncture for neck pain. METHODS: This randomized, patient and assessor-blind, sham-controlled trial was conducted at a Chinese medicine center in Hong Kong between November 2014 and March 2016. A total of 154 eligible participants (age range, 18-65 years) with neck pain were randomly assigned to receive abdominal (n = 77) or non-penetrating sham abdominal (sham group; n = 77) acupuncture. Each participant was administered treatment over six sessions by Registered Chinese Medicine Practitioners, in accordance with a standardized protocol. The primary outcome was mean improvement in neck pain disability scores evaluated by the Northwick Park Neck Pain Questionnaire (NPQ). Secondary outcomes included intensity of neck pain and health-related quality-of-life measures. The outcomes were assessed at baseline and at 2 and 6 weeks from baseline. Patients in the abdominal acupuncture group received additional follow-up evaluation at 14 weeks from baseline. Outcomes were evaluated by intention-to-treat analysis. RESULTS: All participants provided informed consent for treatment and follow-up evaluation. Patients who received abdominal acupuncture exhibited greater improvement in NPQ scores than those who received sham treatment at both 2 and 6 weeks from baseline (intergroup mean differences, -5.75; 95% confidence interval [CI], -9.48 to -2.03; P = 0.008 and -8.65; 95% CI, -12.13 to -5.16; P < 0.001, respectively). The improvement in NPQ scores in the abdominal acupuncture group was even more significant at 14 weeks from baseline. Patients in the abdominal acupuncture group also exhibited significantly greater improvements in intensity of neck pain and a few quality-of-life measures than those in the sham abdominal acupuncture group, without any serious adverse events. CONCLUSION: These findings suggest that abdominal acupuncture is an effective alternative treatment for neck pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-14004932.

Electroacupuncture for older adults with mild cognitive impairment: study protocol for a randomized controlled trial.

BACKGROUND: Mild cognitive impairment is an intermediary state between normal aging and clinical Alzheimer's disease. Early intervention of mild cognitive impairment may be an important strategy in the management of Alzheimer's disease. The proposal aims to evaluate if electroacupuncture would optimize cognitive function in subjects with mild cognitive impairment and understand the role of electroacupuncture in the treatment of Alzheimer's disease. METHODS/DESIGN: A randomised patient- and assessor-blind sham-controlled trial is designed to assess whether electroacupuncture intervention decreases the rate of cognitive decline amongst older adults with mild cognitive impairment. One hundred and fifty subjects aged 65 years of age or over with a diagnosis of mild cognitive impairment are recruited from the community and elderly centre in Hong Kong. All subjects are randomly allocated into two groups (75 subjects each group): the electroacupuncture group and sham control. Participants in the electroacupuncture group receive electroacupuncture stimulation by sterile, disposable acupuncture needles inserted to the acupoints with a depth of 1 to 3 cm. The acupuncture needles are subjected to 2 Hz electroacupuncture with an intensity of 5 to 10 mA. Each participant receives electroacupuncture for 8 weeks (once a day, 3 days a week) and the treatment lasts for 30 minutes each time. For sham electroacupuncture, needles are inserted to a depth of 1 to 2 mm, and connected to the electroacupuncture device without any current passing through. Outcome measures (including primary and secondary outcome measures) are collected at baseline, at the end day of intervention, and months 4 and 6 after intervention. The primary outcome is measured by the Alzheimer Disease Assessment Scale-Cognitive subscale. Secondary outcomes are measured by the mini-mental state examination, category fluency text and the Short Form 12. DISCUSSION: The study will provide evidence for evaluating and understanding the role of electroacupuncture in the treatment of Alzheimer's disease. TRIAL REGISTRATION: This trial is registered with chictr.org (registration number: ChiCTR-TRC-12002414 . Registration date: 11 August 2012.

Antidiabetic Effect of Schisandrae Chinensis Fructus Involves Inhibition of the Sodium Glucose Cotransporter.

Preclinical Research Schisandrae Chinensis Fructus (SCF), the fruit of Schisandra chinensis (Turcz.) Baill. (family Schisandraceae) is traditionally used as a tonic and antidiabetic agent in Asia. In this study, SCF was investigated for its effects on sodium glucose cotransporters 1 and 2 (SGLT 1 and 2) expressed in a COS-7 cell line for its specificity in inhibiting SGLT2, which is a novel mechanism to screen for potential antidiabetic agents. Using a bioassay-guided fractionation, we then tried to isolate and identify the active fraction(s)/component(s). The ethanol extract of SCF at a concentration of 1 mg/mL significantly inhibited 89% of SGLT1 and 73% of SGLT2 activities in a [14 C]-α-methyl-d-glucopyranoside ([14 C]-AMG) uptake assay. Fractionation of the ethanol extract yielded nine fractions, of which F8, at a concentration of 1 mg/mL, was specific in inhibiting SGLT 2 (42% inhibition, P < 0.001), without inhibiting SGLT 1. Using LC/MS-MS, three compounds, deoxyschisandrin, schisandrin B (γ-schisandrin) and schisandrin were identified in F8 and their amounts quantified. However, subsequent evaluation in the [14 C]-AMG uptake assay showed that these three compounds failed to inhibit SGLT 2 activity indicating that the SGLT active component(s) from SCF have yet to be identified. Drug Dev Res 76 : 1-8, 2015.

Tyrosinase inhibitory activity of a glucosylated hydroxystilbene in mouse melan-a melanocytes.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucopyranoside (1), isolated from Polygonum multiflorum, is a noncompetitive inhibitor of tyrosinase in cell-free kinetics; it reduced the Vmax values in a dose-dependent manner. Compound 1 inhibited PKA-induced melanogenesis, reduced the protein expression of tyrosinase and its transcription factor, the microphthalmia-associated transcription factor, and lowered the complex formation between tyrosinase and tyrosinase-related protein 1 (TRP-1). Immunofluorescence microscopy revealed no association of tyrosinase with the endoplasmic reticulum or lysosomes, implying the absence of a direct effect of 1 on the maturation process of the enzyme. The antimelanogenic activity of 1 is likely mediated through a noncompetitive inhibition on tyrosinase, down-regulation of the expression of melanogenic proteins, and reduction of tyrosinase/TRP-1 complex formation.

Photodynamic therapy induced cell death of hormone insensitive prostate cancer PC-3 cells with autophagic characteristics.

BACKGROUND: The introduction of photodynamic therapy (PDT) to the treatment of advanced prostate cancer can accomplish the eradication of local neoplasm and distant metastases with minimized damage to the adjacent structures. The evidence of PDT efficacy for androgen-refractory prostate cancer will be especially meaningful for the patients resistant to hormone therapy. METHODS: Pheophorbide a (PhA) as a photosensitizer was employed to evaluate the photodynamic efficacy in androgen-insensitive PC-3 prostate cancer cells in culture by cell viability assay, reactive oxygen species (ROS) measurement and cell cycle test. Characteristics of apoptosis and autophagy were investigated via DNA fragmentation electrophoresis and immune-fluorescence staining, acidic vesicle determination and detection of LC3B in puncta form by fluorescence microscopy, Western blotting of autophagy-related (Atg) proteins and detailed phenotype shown by electron microscopy. RESULTS: PhA exerted significant photo-cytotoxicity toward androgen-insensitive prostate cancer PC-3 cells in photosensitizer-dose and light-dose dependent manners. The photoactivation immediately initiated hyperproduction of ROS, the depolarization of mitochondrial membrane potential and the arrest of the cell cycle in the G0/G1 phase. Autophagy was revealed in PhA-PDT treated PC-3 cells by a significant high amount of acidic vesicular organelles with acridine orange staining, recruitment of LC3B on the membrane of autophagosomes by fluorescent microscopy, double membrane-bound vesicles suggesting autophagosomes by electron microscopy, significant increased Atg proteins such as beclin-1, Atg12-Atg5 conjugation, Atg7 and the conversion of LC3B-I to LC3B-II by Western blot analysis. CONCLUSIONS: PhA-mediated PDT induced significant autophagy in hormone-refractory prostate cancer PC-3 cells.

Photodynamic effects of pyropheophorbide-a methyl ester in nasopharyngeal carcinoma cells.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common cancers, and exploring novel therapeutic modalities will improve the clinical outcomes. It has been confirmed that photodynamic therapy can efficiently deactivate malignant cells. The aim of the present study was to explore the photodynamic effects of pyropheophorbide-a methyl ester (MPPa) in CNE2 nasopharyngeal carcinoma cells. MATERIAL/METHODS: CNE2 cells were subjected to photodynamic therapy with MPPa, in which the drug concentration was 0.25 to 4 microM and light energy 1 to 8 J/cm(2). Photodynamic toxicity was investigated 24 h after treatment. Apoptosis was determined using flow cytometry with annexin V-FITC and propidum iodine staining and with nuclear staining with Hoechst 33258. The mitochondrial membrane potential (DeltaPsim) was evaluated by Rhodamine 123 assay. RESULTS: There was no dark cytotoxicity of MPPa in the CNE2 cells at doses of 0.25-4 microM, and MPPa resulted in dose- and light-dependent phototoxicity. The apoptotic rate 8 h after PDT with MPPa (2 microM) increased to 16.43% under a light energy of 2 J/cm(2). Mitochondrial membrane potential (DeltaPsim) collapsed when the CNE2 cells were exposed to 2 microM MPPa for 20 h and then 2 J/cm(2) irradiation. CONCLUSIONS: Photodynamic therapy with MPPa significantly enhanced apoptosis and the collapse of DeltaPsim. This can be developed for treating nasopharyngeal carcinoma.