Photodynamic treatment with purpurin 18 effectively inhibits triple negative breast cancer by inducing cell apoptosis.

This study aims to evaluate the photodynamic efficacy of purpurin 18 (pu-18) on triple negative breast cancer both in vitro and in vivo. Two states of 4T1 cells, 2D culture and 3D spheroids, were used to evaluate the photodynamic action of pu-18 in vitro. The in vitro study results indicated that for the 4T1 2D cell culture, the photodynamic therapy (PDT) treatment showed significant photocytotoxicity at low pu-18 concentrations following light irradiation. Pu-18 was found to distribute on the lysosomes, mitochondria, Golgi apparatus, and endoplasmic reticulum. After irradiation, pu-18 can generate ROS to destroy the mitochondrial membrane potential (MMP) and eventually induce apoptosis in the 2D 4T1 cells. Light-activated pu-18 could also induce the destruction of the 3D 4T1 cell spheroids. The in vivo study was conducted by using a subcutaneous 4T1 breast cancer animal model. The results demonstrated that pu-18 could remain in the tumor for more than 4 days by direct intra-tumoral injection. The PDT treatment was performed every 2 days for a total of 3 times. The results showed that PDT treatment could significantly inhibit tumor growth in vivo, indicating a good photodynamic efficacy of pu-18 in the mouse breast cancer model, without influencing weight and major organ function. The survival pattern results showed that PDT treatment could largely extend the survival time of mice with breast cancer. The preliminary conclusion is that photodynamic treatment using pu-18 is effective at preventing the growth of triple negative breast cancer cells both in vitro and in vivo. A combination of light irradiation and pu-18 could therefore be a worthwhile approach for the treatment of triple negative breast cancer.

Effect of photodynamic inactivation of Escherichia coli by hypericin.

The present study has focused on the effects of hypericin (Hyp) based photodynamic inactivation (PDI) of Escherichia coli (E. coli). To evaluate the efficiency of Hyp based PDI of E. coli, single factor experiments and response surface optimization experiment were conducted to obtain the optimum parameter values (36 µM Hyp, 5.9 J cm-2 light dose: 16.4 mW cm-2, 60 W, 260 s, 590 nm and 68 min incubation time) and finally achieved a 4.1 log CFU mL-1 decrease of E. coli. Cell-Hyp interaction and intracellular reactive oxygen species (ROS) level were detected by fluorescence spectrometric photometer. Data indicated that Hyp possessed a strong ability to bind with cells. In addition, a significant increase was observed in intracellular ROS level after Hyp-based photosensitization treatment. Therefore, Hyp-based photosensitization seems to be a promising method to efficiently inactivate E. coli. It is expected to be a safe, efficient, low cost and practical method which can be applied in the field of food safety.

The Size Flexibility of Ferritin Nanocage Opens a New Way to Prepare Nanomaterials.

Ferritins are ubiquitous iron storage proteins where Fe(II) sequestration prevents not only its spontaneous oxidation to Fe(III) but also production of toxic free radicals. Recently, scientists have subverted these nature functions and used ferritin cage structures of nanometer dimensions for encapsulation of guest molecules such as anti-cancer drugs or bioactive nutrients based on pH induced ferritin disassembly and reassembly property. However, prior to this study, ferritin nanocage was required to disassemble only under harsh pH conditions (≤2.0 or ≥11.0), followed by reassembly at near neutral pH. Such harsh conditions can cause protein or guest molecules damage to a great extent during this pH-induced unfolding-refolding process. Here, we provide evidence demonstrating that the apoferritin shell is flexible rather than rigid. Indeed, we found that two large complex molecules, uranyl acetate dihydrate and phosphotungstic acid, can reach the cavity of both plant and animal apoferritin followed by mineralization. Moreover, large organic compound such as curcumin and doxorubicin can also be encapsulated within ferritin cavity by its mixing with protein. This strategy will increase the use of ferritin in nanotechnology, and could be also applicable to other shell-like proteins as templates to prepare nanomaterials.

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 therapy induces apoptosis of human leukemia HL-60 cells in the presence of protoporphyrin IX.

Sonodynamic therapy (SDT) is expected to be a novel therapeutic strategy for tumor. The protoporphyrin IX disodium salt (PpIX), a photosensitizer, can be activated by ultrasound. The present study aims to investigate apoptosis of HL-60 cells induced by PpIX-mediated SDT. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was adopted to examine cell toxicity. Apoptosis was detected using Annexin V-PE/7-amino-actinomycin D (7-AAD) double staining. Detection of apoptotic bodies was examined by Hoechst33342 (HO) staining. Western blotting was used to analyze the protein of caspase-3 and poly ADP-ribose polymerase (PARP). Intracellular reactive oxygen species (ROS) was detected by a flow cytometer after exposures. Compared with PpIX alone and ultrasound alone groups, the synergistic cytotoxicity of PpIX plus ultrasound were significantly boosted. In addition, as determined by Annexin V-PE/7-AAD staining, SDT significantly induced HL-60 cell apoptosis, the obvious nuclear condensation was also found with HO staining at 4 hours post-SDT treatment. Furthermore, Western blotting showed visible enhancement of caspase-3 and PARP cleavage in this process. Besides, intracellular ROS production was significantly enhanced after SDT. Our findings demonstrate that PpIX-mediated SDT could induce apoptosis on HL-60 cells, suggesting that apoptosis is an important mechanism of cell death induced by PpIX-mediated SDT.

Sonodynamic action of hypocrellin B on biofilm-producing Staphylococcus epidermidis in planktonic condition.

Staphylococcus epidermidis is an opportunistic pathogen causing biofilm-associated infections. To investigate sonodynamic action of hypocrellin B on biofilm-producing Staphylococcus epidermidis in planktonic culture, a biofilm-producing strain Staphylococcus epidermidis (ATCC 35984) was incubated with hypocrellin B and then exposed to ultrasound at intensity (ISATA) of 1.56 W/cm(2) with a frequency of 1 MHz in continuous mode for 5 min. After sonodynamic treatment of hypocrellin B, the bacterial growth was measured using the colony counting method. Bacterial membrane integrity was investigated using a flow cytometry with propidium iodide staining. Intracellular reactive oxygen species (ROS) level was measured using a flow cytometry with DCFH-DA staining. The results showed that sonodynamic action of hypocrellin B significantly induced survival reduction of Staphylococcus epidermidis in a hypocrellin B dose-dependent manner, and a 4-log reduction was observed after the combined treatment of hypcorellin B (40 µM) and ultrasound sonication with the intensity of 1.56 W/cm(2) for 5 min. Bacterial membrane integrity was notably damaged and the level of intracellular ROS level was remarkably increased after sonodynamic treatment. The findings demonstrated that sonodynamic action of hypocrellin B had significant antibacterial activity on biofilm-producing Staphylococcus epidermidis in planktonic condition probably through increasing intracellular ROS level to cause damage to bacterial membrane integrity.

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.

Four-fold channels are involved in iron diffusion into the inner cavity of plant ferritin.

From an evolutionary point of view, plant and animal ferritins arose from a common ancestor, but plant ferritin exhibits different features as compared with the animal analogue. One major difference is that the 4-fold channels naturally occurring in plant ferritin are hydrophilic, whereas the 4-fold channels in animal ferritin are hydrophobic. Prior to this study, however, the function of the 4-fold channels in oxidative deposition of iron in phytoferritin remained unknown. To elucidate the role of the 4-fold channels in iron oxidative deposition in ferritin, three mutants of recombinant soybean seed H-2 ferritin (rH-2) were prepared by site-directed mutagenesis, which contained H193A/H197A, a 4-fold channel mutant, E165I/E167A/E171A, a 3-fold channel mutant, and E165I/E167A/E171A/H193A/H197A, where both 3- and 4-channels were mutated. Stopped-flow, electrode oximetry, and transmission electron microscopy (TEM) results showed that H193A/H197A and E165I/E167A/E171A exhibited a similar catalyzing activity of iron oxidation with each other, but a pronounced low activity compared to rH-2, demonstrating that both the 4-fold and 3-fold hydrophilic channels are necessary for iron diffusion in ferritin, followed by oxidation. Indeed, among all tested ferritin, the catalyzing activity of E165I/E167A/E171A/H193A/H197A was weakest because its 3- and 4- fold channels were blocked. These findings advance our understanding of the function of 4-fold channels of plant ferritin and the relationship of the structure and function of ferritin.

Cytotoxic effect of protoporphyrin IX to human Leukemia U937 cells under ultrasonic irradiation.

BACKGROUND: Sonodynamic therapy (SDT) is an alternative strategy that manages malignancies via the generation of cytotoxic factors during ultrasound-activated sono-sensitive agents. However, the detailed mechanisms are not clear. This study was to identify the cytotoxic effects of ultrasound-activated protoporphyrin IX (PpIX) on U937 cells. METHODS: Flow cytometry was performed to detect the time course for PpIX uptake in U937 cells. Sub-cellular localization of PpIX in U937 cells was visualized by inverted confocal laser scanning microscope. Following PpIX-mediated SDT treatment, cell viability was evaluated by the 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay; nuclear damage was observed under fluorescent microscope; DNA fragmentation and mitochondrial membrane potential disruption were measured by flow cytometry. The role of reactive oxygen species (ROS) in SDT-induced cell death was also evaluated. RESULTS: We observed that PpIX is mainly localized in the mitochondria, with a maximal uptake within 2 h. Compared with PpIX or ultrasound alone, PpIX plus ultrasound treatment significantly declined cell viability, caused more serious damage of cell morphology, DNA and mitochondria. In the combined treatment group, the intracellular ROS was greatly higher than in other groups; ROS scavenger N-acetylcysteine could effectively rescue the loss of mitochondria membrane potential and cell viability induced by SDT. CONCLUSION: Taken together, these findings primarily indicated that fatal damage could be induced by PpIX-mediated SDT in U937 cells, and the intracellular ROS was involved during this process. © 2014 S. Karger AG, Basel.

Astragalus (a traditional Chinese medicine) for treating chronic kidney disease.

BACKGROUND: Astragalus (Radix Astragali, huang qi) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. (Family Leguminosae). It is one of the most widely used herbs in traditional Chinese medicine for treating kidney diseases. Evidence is needed to help clinicians and patients make judgments about its use for managing chronic kidney disease (CKD). OBJECTIVES: This review evaluated the benefits and potential harms of Astragalus for the treatment of people with CKD. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 10 July 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We also searched CINAHL, AMED, Current Controlled Trials, OpenSIGLE, and Chinese databases including CBM, CMCC, TCMLARS, Chinese Dissertation Database, CMAC and Index to Chinese Periodical Literature. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing Astragalus, used alone as a crude herb or an extract, with placebo, no treatment, or conventional interventions were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included 22 studies that involved 1323 participants, of whom 241 were receiving dialysis treatment. Risk of bias was assessed as high in six studies, and unclear in the remaining 16 studies. Study quality was low overall.Our nominated primary outcomes of time to requirement for renal replacement therapy (RRT) or initiation of dialysis and all-cause mortality were not reported in any of the included studies.Results concerning the effects of Astragalus on kidney function were inconsistent. Astragalus significantly increased CrCl at end of treatment (4 studies, 306 participants: MD 5.75 mL/min, 95% CI 3.16 to 8.34; I² = 0%), decreased SCr (13 studies, 775 participants: MD -21.39 µmol/L, 95% CI -34.78 to -8; I² = 70%) and especially in those whose baseline SCr was < 133 µmol/L in particular (3 studies, 187 participants: MD -2.52 µmol/l, 95% CI -8.47 to 3.42; I² = 0%). Astragalus significantly decreased 24 hour proteinuria at end of treatment (10 studies, 640 participants; MD -0.53 g/24 h, 95% CI -0.79 to -0.26; I² = 90%); significantly increased haemoglobin levels overall (4 studies, 222 participants): MD 9.51 g/L, 95% CI 4.90 to 14.11; I² = 0%) and in haemodialysis patients in particular (3 studies, 142 participants: MD 11.20 g/L, 95% CI 5.81 to 16.59; I² = 0%). Astragalus significantly increased serum albumin (9 studies, 522 participants: MD 3.55 g/L, 95% CI 2.33 to 4.78; I² = 65%). This significant increase was seen in both dialysis (3 studies, 152 participants): MD 4.04 g/L, 95% CI 1.91 to 6.16; I² = 72%) and non-dialysis patients (6 studies, 370 participants: MD 3.24 g/L, 95% CI 1.70 to 4.77; I² = 61%). Astragalus significantly decreased systolic blood pressure (2 studies, 77 participants: MD -16.65 mm Hg, 95% CI -28.83 to -4.47; I² = 50%), and diastolic blood pressure (2 studies, 77 participants: MD -6.02 mm Hg, 95% CI -10.59 to -1.46; I² = 0%).Six of 22 included studies reported no adverse effects were observed; while the remaining 16 studies did not report adverse effects. AUTHORS' CONCLUSIONS: Although Astragalus as an adjunctive treatment to conventional therapies was found to offer some promising effects in reducing proteinuria and increasing haemoglobin and serum albumin, suboptimal methodological quality and poor reporting meant that definitive conclusions could not be made based on available evidence.

Effect of ultrasound sonication on clonogenic survival and mitochondria of ovarian cancer cells in the presence of methylene blue.

OBJECTIVES: This study aimed to investigate the effect of ultrasound sonication in the presence of methylene blue on clonogenic survival and mitochondria of ovarian cancer cells. METHODS: Human ovarian cancer HO-8910 cells, which were incubated with different concentrations of methylene blue for 1 hour, were exposed to an ultrasonic wave for 5 seconds with intensity of 0.46 W/cm(2). Clonogenic survival of HO-8910 cells after ultrasound sonication was measured by a colony-forming unit assay. Mitochondrial structural changes were observed on transmission electron microscopy, and the mitochondrial membrane potential was evaluated by confocal laser-scanning microscopy with rhodamine 123 staining. RESULTS: The colony-forming units of HO-8910 cells decreased considerably after ultrasound sonication in the presence of methylene blue. Transmission electron microscopy showed slightly enlarged mitochondria in the ultrasound-treated cells in the absence of methylene blue; however, seriously damaged mitochondria, even with almost complete disappearance of cristae, were found in the cells treated by ultrasound sonication in the presence of methylene blue. The mitochondrial membrane potential collapsed significantly when HO-8910 cells were treated by ultrasound sonication in the presence of methylene blue (P < .05). CONCLUSIONS: Ultrasound sonication in the presence of methylene blue markedly damaged mitochondrial structure and function and decreased clonogenic survival of HO-8910 cells.

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.

A one-two punch strategy for diabetic wound management based on an antibiotic-hybrid biomineralized iron sulfide nanoparticle.

Bacterial infection and immune imbalance are the primary culprits behind chronic wounds in individuals with diabetes, impeding the progression of damaged tissues towards normal healing. To achieve a harmonious balance between pro- and anti-inflammation within these infected areas, herein, we propose a one-two punch strategy for on-demand therapy of diabetes-infected wounds, utilizing an azithromycin (AZM)-hybrid nanocomposite termed GOx@FexSy/AZM. During the infective stage, the nanocomposite facilitates the production of ROS, coupled with the burst release of AZM and H2S gas, effectively dismantling biofilms and achieving rapid sterilization. Subsequently, the hyperinflammatory response induced by antibiosis is significantly mitigated through the synergistic action of tissue H2S and the prolonged half-life of AZM. These components inhibit the activity of pro-inflammatory transcription factors (AP-1 and NF-κB) within macrophages, thereby promoting the polarization of macrophages towards a reparative M2 phenotype and facilitating tissue remodeling. By catering to the diverse requirements of wound healing at different stages, this nanocomposite accelerates a sensible transition from inflammation to the reparative phase. In summary, this one-two punch strategy gives an instructive instance for procedural treatment of diabetes wound infection. STATEMENT OF SIGNIFICANCE: The treatment of diabetic wound infection presents two major challenges: the diminished antibacterial efficacy arising from biofilm formation and bacterial resistance, as well as the inadequate transition of the wound microenvironment from pro-inflammatory to anti-inflammatory states after bacterial clearance. In this work, a biomineralized iron sulfide nanocomposite was prepared to mediate cascade catalytic (ROS storm) / antibiotic (AZM) / gas (H2S) triple-synergetic antibacterial therapy during the initial stage of bacterial infection, achieving the goal of rapid bactericidal effect; Subsequently, the residual H2S and long half-life AZM would inhibit the key pro-inflammatory transcription factors and promote the macrophages polarization to reparative M2, which effectively mediated tissue repair after hyperinflammatory reactions, leading to orderly treatment of hyperglycemic infected wounds.

Hot-Pressing Metal Covalent Organic Frameworks as Personal Protection Films.

Effective personal protection is crucial for controlling infectious disease spread. However, commonly used personal protective materials such as disposable masks lack antibacterial/antiviral function and may lead to cross infection. Herein, a polyethylene glycol-assisted solvent-free strategy is proposed to rapidly synthesize a series of the donor-acceptor metal-covalent organic frameworks (MCOFs) (i.e., GZHMU-2, JNM-1, and JNM-2) under air atmosphere and henceforth extend it via in situ hot-pressing process to prepare MCOFs based films with photocatalytic disinfect ability. Best of them, the newly designed GZHMU-2 has a wide absorption spectrum (200 to 1500 nm) and can efficiently produce reactive oxygen species under sunlight irradiation, achieving excellent photocatalytic disinfection performance. After in situ hot-pressing as a film material, the obtained GZHMU-2/NMF can effectively kill E. coli (99.99%), S. aureus (99%), and H1N1 (92.5%), meanwhile possessing good reusability. Noteworthy, the long-term use of a GZHMU-2/NWF-based mask has verified no damage to the living body by measuring the expression of mouse blood routine, lung tissue, and inflammatory factors at the in-vivo level.

Lovastatin/SN38 co-loaded liposomes amplified ICB therapeutic effect via remodeling the immunologically-cold colon tumor and synergized stimulation of cGAS-STING pathway.

Current immune checkpoint blockade (ICB) immunotherapeutics have revolutionized cancer treatment. However, many cancers especially the "immunologically cold" tumors, do not respond to ICB, prompting the search for additional strategies to achieve durable responses. The cGAS-STING pathway, as an essential immune response pathway, has been demonstrated for a potent target to sensitize ICB immunotherapy. However, the low efficiency of conventional STING agonists limits their clinical application. Recent studies have shown that DNA topoisomerase I (TOPI) inhibitor chemodrug SN38 can activate the cGAS-STING pathway and induce an immune response through DNA damage, while the traditional statins medication lovastatin was found to inhibit DNA damage repair, which may in turn upregulate the damaged DNA level. Herein, we have developed a liposomal carrier co-loaded with SN38 and lovastatin (SL@Lip), which can be accumulated in tumors and efficiently released SN38 and lovastatin, addressing the problem of weak solubility of these two drugs. Importantly, lovastatin can increase DNA damage and enhance the activation of cGAS-STING pathway, coordinating with SN38 chemotherapy and exhibiting the enhanced combinational immunotherapy of PD-1 antibody by remodeling the tumor microenvironment in mouse colorectal cancer of both subcutaneous and orthotopic xenograft models. Overall, this study demonstrates that lovastatin-assisted cGAS-STING stimulation mediated by liposomal delivery system significantly strengthened both chemotherapy and immunotherapy of colorectal cancer, providing a clinically translational strategy for combinational ICB therapy in the "immunologically cold" tumors.

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.

Cocrystallization of Gefitinib Potentiate Single-Dose Oral Administration for Lung Tumor Eradication via Unbalancing the DNA Damage/Repair.

Gefitinib (GEF) is a clinical medication for the treatment of lung cancer targeting the epidermal growth factor receptor (EGFR). However, its efficacy is remarkably limited by low solubility and dissolution rates. In this study, two cocrystals of GEF with co-formers were successfully synthesized using the recrystallization method characterized via Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and 2D Nuclear Overhauser Effect Spectroscopy. The solubility and dissolution rates of cocrystals were found to be two times higher than those of free GEF. In vitro cytotoxicity studies revealed that the cocrystals enhanced the inhibition of cell proliferation and apoptosis in A549 and H1299 cells compared to free GEF. In mouse models, GEF@TSBO demonstrated targeted, safe, and effective antitumor activity with only one-dose administration. Mechanistically, the GEF cocrystals were shown to increase the cellular levels of damaged DNA, while potentially downregulating PARP, thereby impairing the DNA repair machinery and leading to an imbalance between DNA damage and restoration. These findings suggest that the cocrystallization of GEF could serve as a promising adjunct to significantly enhance the physicochemical and biopharmaceutical performance for lung cancer treatment, providing a facial strategy to improve GEF anticancer efficiency with high bioavailability that can be orally administrated with only one dose.

A scientometrics study of the nanomedicines assisted in respiratory diseases.

Nanomedicine has been extensively studied for its versatility and broad-spectrum applications of theranostics in the research of respiratory disease. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on nanomedicine applied in the research of respiratory disease has not been reported so far, which would be of major importance to relevant researchers. To explore and exhibit the research status and developing trend of nanomedicines deployed in basic or clinical research in respiratory disease, the research ecosystem and exciting subareas were profiled based on the massive data mining and visualization from the relevant works reported from 2006 to 2021. Data were collected from the Web of Science database. Data statistics software and bibliometric analysis software were employed to visualize the research trend and the relationship between respiratory diseases and nanomedicines in each representative direction. The cluster analysis and burst detections indicated that the improvement of drug delivery and vaccine developments are the up-to-date key directions in nanomedicines for respiratory disease research and treatments. Furthermore, we emphatically studied four branch areas in this field including COVID-19, nanotube, respiratory syncytial virus, and mRNA vaccine those are selected for in-depth mining and bibliometric coupling analysis. Research trends signify the future focuses will center on preventing respiratory diseases with mRNA vaccines using nanoparticle-based approaches. We anticipate our study will enable researchers to have the panorama and deep insights in this area, thus inspiriting further exploitations especially the nanobiomaterial-based systems for theranostic applications in respiratory disease treatment.

Evolutionary Trend Analysis of Research on 5-ALA Delivery and Theranostic Applications Based on a Scientometrics Study.

5-aminolevulinic acid (5-ALA) has been extensively studied for its sustainability and broad-spectrum applications in medical research and theranostics, as well as other areas. It's a precursor of protoporphyrin IX (PpIX), a sustainable endogenous and naturally-existing photosensitizer. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on 5-ALA research has not been reported so far, which would be of major importance to the relevant researchers. In this study, we collected all the research articles published in the last two decades from the Web of Science Core Collection database and employed bibliometric methods to comprehensively analyze the dataset from different perspectives using CiteSpace. A total of 1595 articles were identified. The analysis results showed that China published the largest number of articles, and SBI Pharmaceuticals Co., Ltd. was the most productive institution that sponsored several of the most productive authors. The cluster analysis and burst detections indicated that the improvement of photodynamic efficacy theranostics is the up-to-date key direction in 5-ALA research. Furthermore, we emphatically studied nanotechnology involvement in 5-ALA delivery and theranostics research. We envision that our results will be beneficial for researchers to have a panorama of and deep insights into this area, thus inspiring further exploitations, especially of the nanomaterial-based systems for 5-ALA delivery and theranostic applications.

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.