5-aminolevulinic acid photodynamic therapy for chronic wound infection in rats with diabetes.

Recent research indicated that ulcers and peripheral vascular disease resulting from drug-resistant bacterial infections are the main causes of delayed healing in chronic diabetic wounds. 5-Aminolevulinic acid (ALA) is a second-generation endogenous photosensitizer. The therapeutic effect and mechanism of ALA-mediated photodynamic therapy (ALA-PDT) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic rats were investigated in this study. The results revealed the promising antibacterial effects of ALA-PDT MRSA in vitro, with a minimum inhibitory concentration and minimum bactericidal concentration of 250 and 500 µM, respectively. ALA-PDT also changed the permeability and structural integrity of bacterial cell membranes by producing reactive oxygen species. Meanwhile, ALA-PDT accelerated wound healing in MRSA-infected diabetic rats, with 5 % ALA-PDT achieving complete sterilization in 14 days and wound closure in 21 days. Treatment with 5 % ALA-PDT additionally improved the histopathological appearance of skin tissue, as well as fibrosis, inflammatory cytokine release, and angiogenesis-related protein expression. These findings indicated that ALA-PDT significantly promoted the healing of MRSA-infected wounds in diabetic rats by eliminating bacteria, inhibiting inflammation, generating granulation tissues, promoting neovascularization, and restoring damaged nerves. In addition, the healing mechanism was related to the activation of inflammatory and angiogenesis pathways through the regulation of tumor necrosis factor-alpha and interleukin-6 expression and upregulation of CD206, CD31, and VEGF. These findings underscored the potential role of ALA-PDT in promoting the healing of chronic diabetic wounds.

Evaluation of antibacterial effect of a cationic porphyrin derivative on Pseudomonas aeruginosa in photodynamic therapy.

BACKGROUND: Pseudomonas aeruginosa is a gram-negative bacterium without spores, and it is one of the pathogens that easily cause secondary infectious diseases when human immune function is low. The purpose of this study is to explore the inhibitory effect of photodynamic antibacterial chemotherapy-induced by cationic porphyrin derivative on clinical P. aeruginosa and its mechanism. METHODS: The uptake of photosensitizer by P. aeruginosa and L929 cells was measured by an ultraviolet spectrophotometer. Effect of laser energy density on the bacterial activity of P. aeruginosa and post antibiotic effect were measured by bacterial suspension and tenfold dilution method. Flow cytometry and scanning electron microscopy were used to observe the activity and morphological changes of P. aeruginosa after PACT treatment. RESULTS: The uptake of Tetra-ATPP-Lys-by P. aeruginosa and L929 was shown as concentration-dependent and time-dependent. However the uptake of L929 cell had a clear difference with P. aeruginosa at the same time and concentration intervals(P < 0.05).The increasing laser energy density had a high inactivation effect of on P. aeruginosa at the same Tetra-ATPP-Lys-concentration(P < 0.05). Post-antibiotic effect of Tetra-ATPP-Lys -PACT was dose-dependent(P < 0.05). Bacterial viability which evaluated by the flow cytometry method demonstrated that the proportion of viable bacteria is decreased with the photosensitizer dose-dependent. The morphology and microstructure of P. aeruginosa after Tetra-ATPP-Lys -PACT was demonstrated by a scanning electron microscope(SEM). After PACT, the morphology of P. aeruginosa was rod-shaped, the outer membrane surface was rough, and the bacteria were dry flat, sunken, shrunk and deformed. CONCLUSIONS: Cationic porphyrin photosensitizer had a great damage effect on P. aeruginosa under the PACT, which can effectively destroy the microstructure of bacteria and lead to bacterial inactivation and death.

Toxicity of the Mycotoxin Deoxynivalenol on Early Cleavage of Mouse Embryos by Fluorescence Intensity Analysis.

Deoxynivalenol is a mycotoxin, produced by Fusarium from contaminated corn, wheat, and other grains, that induces multiple effects in humans and animals, including cytotoxic, genotoxic, immunotoxic, and carcinogenic effects. Recent studies show that deoxynivalenol also affects the reproductive system of mammals, including oocyte quality. However, the effects of deoxynivalenol on early embryonic development have not been reported. In this study, fluorescence intensity analysis was used to show that deoxynivalenol disrupted the first cleavage of the zygote. The high deoxynivalenol dose disturbed the movement of the pronucleus after fertilization, while the low deoxynivalenol dose caused aberrant spindle morphology during the metaphase of the first cleavage. Further analysis showed that the reactive oxygen species level increased in the deoxynivalenol-exposed two-cell embryos, indicating oxidative stress. Moreover, deoxynivalenol caused DNA damage in the embryos, as positive γH2A.X signals were detected in the nucleus. These events led to the early apoptosis of mouse embryos, which was confirmed by autophagy. Taken together, our study provides evidence for the toxicity of deoxynivalenol during early embryonic development in the mouse model.

Aflatoxin B1 impairs porcine oocyte quality via disturbing intracellular membrane system and ATP production.

Aflatoxin is the most common type of mycotoxins in contaminated corn, peanuts and rice, which affects the livestock and ultimately endangers human health. Aflatoxin is reported to have carcinogenicity, mutation, growth retardation, immunosuppression and reproductive toxicity. In present study we reported the causes for the declined porcine oocyte quality under aflatoxin exposure. We set up an in vitro exposure model and showed that aflatoxin B1 disturbed cumulus cell expansion and oocyte polar body extrusion. We found that aflatoxin B1 exposure disrupted ER distribution and elevated the expression of GRP78, indicating the occurrence of ER stress, and the increased calcium storage also confirmed this. Besides, the structure of cis-Golgi apparatus, another intracellular membrane system was also affected, showing with decreased GM130 expression. The oocytes under aflatoxin B1 exposure showed aberrant lysosome accumulation and higher LAMP2 expression, a marker for lysosome membrane protection, and this might be due to the aberrant mitochondria function with low ATP production and the increase of apoptosis, since we found that BAX expression increased, and ribosomal protein which is also an apoptosis-related factor RPS3 decreased. Taken together, our study revealed that aflatoxin B1 impairs intracellular membrane system ER, Golgi apparatus, lysosome and mitochondria function to affect porcine oocyte maturation quality.

A Novel Paclitaxel Derivative for Triple-Negative Breast Cancer Chemotherapy.

Paclitaxel-triethylenetetramine hexaacetic acid conjugate (PTX-TTHA), a novel semi-synthetic taxane, is designed to improve the water solubility and cosolvent toxicity of paclitaxel in several aminopolycarboxylic acid groups. In this study, the in vitro and in vivo antitumor effects and mechanisms of PTX-TTHA against triple-negative breast cancer (TNBC) and its intravenous toxicity were evaluated. Results showed the water solubility of PTX-TTHA was greater than 5 mg/mL, which was about 7140-fold higher than that of paclitaxel (<0.7 µg/mL). PTX-TTHA (10-105 nmol/L) could significantly inhibit breast cancer proliferation and induce apoptosis by stabilizing microtubules and arresting the cell cycle in the G2/M phase in vitro, with its therapeutic effect and mechanism similar to paclitaxel. However, when the MDA-MB-231 cell-derived xenograft (CDX) tumor model received PTX-TTHA (13.73 mg/kg) treatment once every 3 days for 21 days, the tumor inhibition rate was up to 77.32%. Furthermore, PTX-TTHA could inhibit tumor proliferation by downregulating Ki-67, and induce apoptosis by increasing pro-apoptotic proteins (Bax, cleaved caspase-3) and TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and reducing anti-apoptotic protein (Bcl-2). Moreover, PTX-TTHA demonstrated no sign of acute toxicity on vital organs, hematological, and biochemical parameters at the limit dose (138.6 mg/kg, i.v.). Our study indicated that PTX-TTHA showed better water solubility than paclitaxel, as well as comparable in vitro and in vivo antitumor activity in TNBC models. In addition, the antitumor mechanism of PTX-TTHA was related to microtubule regulation and apoptosis signaling pathway activation.

Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins.

A series of small-molecule fluoroquinolones were synthesized, characterized by HRMS and NMR spectroscopy, and screened for their antibacterial activity against MRSA, P. aeruginosa, and E. coli as model G+/G- pathogens. Compounds 2-e, 3-e, and 4-e were more potent than the reference drug balofloxacin against MRSA and P. aeruginosa (MIC values of 0.0195 and 0.039 µg/ml for 2-e, 0.039 and 0.078 µg/ml for each of 3-e and 4-e, respectively). Analysis of the time-dependent antibacterial effect of compound 2-e toward MRSA showed that in the early logarithmic growth phase, bactericidal effects occurred, while in the late logarithmic growth phase, bacterial inhibition occurred because of concentration effects and possibly the development of drug resistance. Compound 2-e exhibited low toxicity toward normal mammalian cell lines 3T3 and L-02 and tumor cell lines A549, H520, BEL-7402, and MCF-7. The compound was not hemolytic. Atomic force microscopy (AFM) revealed that compound 2-e could effectively destroy the membrane and wall of MRSA cells, resulting in the outflow of the cellular contents. Docking studies indicated the good binding profile of these compounds toward DNA gyrase and topoisomerase IV. ADMET's prediction showed that most of the synthesized compounds followed Lipinski's "rule of five" and possessed good drug-like properties. Our data suggested that compound 2-e exhibited potent anti-MRSA activity and is worthy of further investigation.

Synthesis and Discovery of Ligustrazine-Heterocycle Derivatives as Antitumor Agents.

Ligustrazine (TMP) is a natural pyrazine alkaloid extracted from the roots of Ligusticum Chuanxiong Hort, which has the potential as an antitumor agent. A series of 33 ligustrazine-heterocycle (TMPH) derivatives were designed, synthesized, and investigated via antitumor screening assays, molecular docking analysis, and prediction of drug-like properties. TMP was attached to other heterocyclic derivatives by an 8-12 methylene alkyl chain as a linker to obtain 33 TMPH derivatives. The structures were confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectroscopy spectral (HR-MS) data. The antiproliferative activity against human breast cancer MCF-7, MDA-MB-231, mouse breast cancer 4T1, mouse fibroblast L929, and human umbilical vein endothelial HUVEC cell lines was evaluated by MTT assay. Compound 12-9 displayed significant inhibitory activity with IC50 values in the low micromolar range (0.84 ± 0.02 µM against the MDA-MB-231 cell line). The antitumor effects of compound 12-9 were further evaluated by plate cloning, Hoechst 33 342 staining, and annexin V-FITC/PI staining. The results indicated that compound 12-9 inhibited the proliferation and apoptosis of breast cancer cells. Furthermore, molecular docking of compound 12-9 into the active site of the Bcl-2, CASP-3, and PSMB5 target proteins was performed to explore the probable binding mode. The 33 newly synthesized compounds were predicted to have good drug-like properties in a theoretical study. Overall, these results indicated that compound 12-9 inhibited cell proliferation through PSMB5 and apoptosis through Bcl-2/CASP-3 apoptotic signaling pathways and had good drug-like properties. These results provided more information, and key precursor lead derivatives, in the search for effective bioactive components from Chinese natural medicines.

Self-assembled morphologies of polyelectrolyte-grafted nanoparticles directed by oppositely charged polymer matrices.

Self-assembled structure of polymer grafted nanoparticles is an interesting and growing subject in the field of hybrid electronics and high energy density materials. In light of this, the self-assembled morphologies of polyelectrolyte (PE) sparsely grafted nanoparticles tuned by oppositely charged matrix chains are studied using molecular dynamics simulations. Our focus is to elucidate the effect of matrix chain polymerization on modulating the stretching properties of tethered PE layers, on the self-assembled structuring of nanoparticles. Through varying the matrix chain length and stiffness as well as electrostatic interaction strength, rich phase behaviors of PE coated nanoparticles are predicted, including spherical micelle-like structures being preferred with short matrix chains and percolating network morphologies favored with long matrix chains, which is more pronounced with an enhanced matrix chain rigidness. To pinpoint the mechanisms of self-assembled structure formation, the thickness of grafted layers, the gyration radius of tethered chains, and pair correlation functions between nanoparticles are analyzed carefully. Additionally, electrostatic correlations, manifested as the bridging via matrix chains, are examined by identifying three states of matrix PE chains. Our simulation results may be useful for designing smart polymer nanocomposites based on PE coated nanoparticles.

Nonylphenol exposure-induced oocyte quality deterioration could be reversed by melatonin supplementation in mice.

Nonylphenol (NP) belongs to the metabolites of commercial detergents, which acts as an environmental endocrine disruptor. NP is reported to have multiple toxicity including reproductive toxicity. In present study, we reported the protective effects of melatonin on the NP-exposed oocyte quality. We set up a mouse in vivo model of NP exposure (500 µg/L), by daily drinking and continued feeding for 4 weeks; and we gave a daily dose of melatonin (30 mg/kg) to the NP-exposed mice. Melatonin supplementation restores the development ability of oocytes exposed to NP, and this was due to the reduction of ROS level and DNA damage by melatonin. Melatonin could rescue aberrant mitochondria distribution, mitochondria membrane potential, which also was reflected by ATP content and mtDNA copy number. Moreover, melatonin could restore the RPS3 expression to ensure the ribosome function for protein synthesis, and reduced GRP78 protein level to protect against ER stress and ER distribution defects. We also found that vesicle protein Rab11 from Golgi apparatus was protected by melatonin at the spindle periphery of oocytes of NP-exposed mice, which further moderated LAMP2 for lysosome function. Our results indicate that melatonin protects oocytes from NP exposure through its effects on the reduction of oxidative stress and DNA damage, which might be through its amelioration on the organelles in mice.

Study of nuclear modification factors of deuteron and anti-deuteron in Pb-Pb collisions at [Formula: see text].

The nuclear modification factors ([Formula: see text]) of d and [Formula: see text] have been studied using the parton and hadron cascade model plus the dynamically constrained phase space coalescence model in peripheral (40-60%) and central (0-5%) Pb-Pb collisions at [Formula: see text] with [Formula: see text]. It is found that the [Formula: see text] of [Formula: see text] is similar to that of hadrons ([Formula: see text]) and the [Formula: see text] of antiparticles is the same as that of particles. The suppression effect of d is more significant than that of baryons and mesons in the high-[Formula: see text] region. The suppression of [Formula: see text] at high-[Formula: see text] strongly depends on event centrality and mass of the particles, i.e., the central collision is more suppressed than the peripheral collision. Besides, the yield ratios and double ratios for different particle species, and the coalescence parameter [Formula: see text] for ([Formula: see text]) in pp and Pb-Pb collisions are discussed, respectively. It is observed that the yield ratios and double ratios of d to p and p to [Formula: see text] are similar to those of their anti-particles in three different collision systems, suggesting that the suppressions of matter ([Formula: see text]) and the corresponding antimatter ([Formula: see text]) are around the same level.

Exposure to nonylphenol impairs oocyte quality via the induction of organelle defects in mice.

Nonylphenol (NP) is an environmental endocrine disruptor, which is mainly used in the production of surfactants, lubricants, additives, pesticides, and emulsifiers. NP is widely found in sewage and sludge, which has neurotoxicity, immunotoxicity, metabolic toxicity and reproductive toxicity. In this study, we investigated the effects of NP exposure on mammalian oocyte quality from organelle aspects with mouse in vivo model. The results showed that the ovarian weight of mice exposed to 500 µg/L NP for 4 weeks increased and the development ability of oocytes decreased, showing with lower rate of polar body extrusion. Further analysis indicated that exposure to NP caused the abnormal distribution of mitochondria, following with altered membrane potential drop. NP exposure disrupted the spindle periphery localization of ER, and affected the expression of GRP78 for the induction of ER stress. Moreover, Golgi apparatus fragment in the oocytes was observed, and Rab11-based vesicle transport was disturbed. We also found that the protein degradation might be affected since LAMP2 expression increased and LC3 decreased, indicating the lysosome and autophagy dysfunction. Taken together, our findings suggested that the exposure of NP to mice in vivo affected oocyte quality through its effects on the distribution and function of organelles.

Mapping of dwarfing QTL of Ari1327, a semi-dwarf mutant of upland cotton.

BACKGROUND: Upland Cotton (Gossypium hirsutum L.) has few cotton varieties suitable for mechanical harvesting. The plant height of the cultivar is one of the key features that need to modify. Hence, this study was planned to locate the QTL for plant height in a 60Co γ treated upland cotton semi-dwarf mutant Ari1327. RESULTS: Interestingly, bulk segregant analysis (BSA) and genotyping by sequencing (GBS) methods exhibited that candidate QTL was co-located in the region of 5.80-9.66 Mb at D01 chromosome in two F2 populations. Using three InDel markers to genotype a population of 1241 individuals confirmed that the offspring's phenotype is consistent with the genotype. Comparative analysis of RNA-seq between the mutant and wild variety exhibited that Gh_D01G0592 was identified as the source of dwarfness from 200 genes. In addition, it was also revealed that the appropriate use of partial separation markers in QTL mapping can escalate linkage information. CONCLUSIONS: Overwhelmingly, the results will provide the basis to reveal the function of candidate genes and the utilization of excellent dwarf genetic resources in the future.

Metabolomic Study on Iohexol-Induced Nephrotoxicity in Rats Based on NMR and LC-MS Analyses.

Iohexol, the raw material of nonionic X-ray computed tomography (X-CT) contrast medium, is usually injected into the vein before CT angiography diagnosis. It is used for angiography, urography, and lymphography. With the advantages of low contrast density and good tolerance, it is currently one of the most popular contrast media. However, the renal toxicity of iohexol seriously affects its safety use. Therefore, it is of great importance to identify new potential diagnostic biomarkers and therapeutic targets in the process of contrast medium-induced acute kidney injury (CI-AKI) in order to safely use iohexol in clinical practice. In this study, in order to understand the metabolic mechanism of CI-AKI, ultra-high-performance liquid chromatography/quadrupole-Orbitrap-mass spectrometry and 1H NMR-based metabolomic techniques were utilized to study the metabolic spectra of kidney, plasma, and urine from CI-AKI rats, and a total of 30 metabolites that were closely related to kidney injury were screened out, which were mainly related to 9 metabolic pathways. The results further indicated that iohexol might intensify kidney dysfunction in vivo by disrupting the metabolic pathways in the body, especially through blocking energy metabolism, amino acid metabolism, and promoting inflammatory reactions.

Prevalence and Impact Factors of COVID-19 Vaccination Hesitancy Among Breast Cancer Survivors: A Multicenter Cross-Sectional Study in China.

Cancer patients are at a high risk of being infected with COVID-19 and have a poor prognosis after infection. Breast cancer is one of the most common cancers. Since vaccination is an effective measure to prevent the spread of COVID-19, we studied the vaccination rate among breast cancer survivors and analyzed their characteristics to provide evidence for boosting the vaccination rate. The researchers conducted a multicenter, cross-sectional study on 747 breast cancer survivors from six hospitals in Wuhan city between June 5, 2021, and June 12, 2021. The self-administrated questionnaires based on relevant studies were distributed. The researchers then compared differences in characteristics among vaccinated patients, hesitant patients, and non-vaccinated patients. Moreover, they performed univariable and multivariable logistic regression analyses to identify potential factors associated with vaccination hesitancy. The researchers assessed a total of 744 breast cancer survivors -94 cases in the vaccinated group, 103 in the planning group, 295 in the hesitancy group, and 252 in the refusal group. The vaccination rate was 12.63% (95% CI 10.25-15.02%) and 37.23% (95% CI 27.48-47.82%) patients reported adverse reactions. The vaccination hesitancy/refusal rate was 73.52% (95% CI 70.19-76.66%), which was independently associated with current endocrine or targeted therapy (odds ratio [OR] = 1.52, 95% CI 1.03-2.24), no notification from communities or units (OR = 2.46, 95% CI 1.69-3.59) and self-perceived feel (general vs. good, OR = 1.46, 95% CI 1.01-2.13; bad vs. good, OR = 4.75, 95% CI 1.85-12.16). In the hesitancy/refusal group, the primary reason was "I did not know who to ask whether I can get vaccinated" (46.07%), the person who would most influence decisions of patients was the doctor in charge of treatment (35.83%). Effective interaction between doctors and patients, simple and consistent practical guidelines on vaccination, and timely and positive information from authoritative media could combat misinformation and greatly reduce vaccine hesitancy among breast cancer survivors.

Photodynamic Therapy of Novel Photosensitizer Ameliorates TNBS-Induced Ulcerative Colitis via Inhibition of AOC1.

Ulcerative colitis (UC), a chronic, nonspecific inflammatory bowel disease characterized by continuous and diffuse inflammatory changes in the colonic mucosa, requires novel treatment method. Photodynamic therapy (PDT), as a promising physico-chemical treatment method, were used to treat UC rats' model with novel photosensitizer LD4 in this paper, the treatment effect and mechanism was investigated. LD4-PDT could improve the survival rate of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC model rats, decrease expression of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), myeloperoxidase (MPO) and increase the expression of glutathione (GSH) and superoxide oxidase (SOD), while protecting the integrity of the intestinal epithelium. LD4-PDT treatment could rebuild the intestinal microflora composition and reprogram the colonic protein profiles in TNBS-induced rats to almost the normal state. Proteomics analysis based upon TNBS-induced UC model rats revealed that Amine oxidase copper-containing 1 (AOC1) was a potential target of LD4-PDT. Novel photosensitizer agent LD4-PDT represents an efficient treatment method for UC, and AOC1 may be a promising target.

Methoxypolyethylene Glycol-Substituted Zinc Phthalocyanines for Multiple Tumor-Selective Fluorescence Imaging and Photodynamic Therapy.

Highly tumor-tissue-selective drugs are a prerequisite for accurate diagnosis and efficient photodynamic therapy (PDT) of tumors, but the currently used fluorescent dyes and photosensitizers generally lack the ability for high accumulation and precise localization in tumor tissues. Here we report that monomethoxy polyethylene glycol (MPEG)-modified zinc phthalocyanine (ZnPc) can be selectively accumulated in multiple tumor tissues, and that the selectivity is controlled by the chain length of MPEG. MPEG-monosubstituted ZnPcs with different chain lengths were synthesized, among which the shorter chain (mw < 2k)-modified ZnPc did not show tumor tissue selectivity, while MPEG2k-5k-substituted ZnPc could be rapidly and selectively accumulated in H22 tumor tissues in mice after intravenous injection. Especially, MPEG4k-Pc showed the best tumor tissue selectivity with a tumor/liver (T/L) ratio of 1.7-2.2 in HepG2, MDA-MB231, AGS, and HT-29 tumor-bearing mice. It also exhibited potent photodynamic therapy effects after one PDT treatment, and tumor growth was significantly inhibited in H22-bearing mice with an inhibition rate over 98% and no obvious toxicity. Consequently, MPEG-modified ZnPc could serve as a potential platform for selective fluorescence imaging and photodynamic therapy of multiple tumors.

Corrigendum: A Novel Antioxidant Protects Against Contrast Medium-Induced Acute Kidney Injury in Rats.

[This corrects the article DOI: 10.3389/fphar.2020.599577.].

Antimicrobial Photodynamic Therapy Combined With Antibiotic in the Treatment of Rats With Third-Degree Burns.

Cationic porphyrin conjugate, protoporphyrin IX-methyl ethylenediamine derivative (PPIX-MED) has a potent photosensitive antibacterial effect on clinically isolated bacteria, including methicillin-resistant Staphylococcus aureus, (MRSA), Escherichia coli, and Pseudomonas aeruginosa. This study investigated (i) the PPIX-MED-mediated antimicrobial photodynamic effect on these three species in vitro and (ii) the effect of antimicrobial photodynamic therapy (aPDT) combined with the use of an antibiotic on the healing in vivo of third-degree burns of rats with the wounds infected by these bacterial species. PPIX-MED exerted a potent inhibitory effect on the growth of the three bacterial species by producing reactive oxygen species when photoactivated. PPIX-MED-mediated antimicrobial photodynamic therapy (PPIX-MED-aPDT) had high bacterial photoinactivation ability in vitro, with a minimum inhibitory concentration of 15.6 µM PPIX-MED against each of the three types of bacteria and minimum bactericidal concentrations of 31.25 µM against MRSA and E. coli and 62.5 µM against P. aeruginosa. In rats with third-degree burns infected by a mixture of these bacteria, the bactericidal efficiency of PPIX-MED-aPDT-combined-with-antibiotic treatment was higher than that of antibiotic or aPDT treatment alone. This was confirmed by analysis of viable bacterial counts in wound tissue and blood. Enzyme-linked immunosorbent assay revealed that aPDT-combined-with-antibiotic treatment resulted in an obvious reduction in tumor necrosis factor-alpha and interleukin-6 levels compared with the no-treatment control group and the other treatment groups. Immunohistochemistry revealed that the expression of basic fibroblast growth factor and CD31 (a marker of neovascularization), expressed in burn wound tissue was higher in the aPDT-combined-with-antibiotic treatment group than in the other groups. PPIX-MED-aPDT has a promising bactericidal effect both in vitro and in vivo, and PPIX-MED-aPDT-combined-with-antibiotic treatment enhanced the healing of infected third-degree burns in rats.

Clinical value of digital tomographic fusion imaging in the diagnosis of avascular necrosis of the femoral head in adults.

BACKGROUND: To explore the clinical significance of digital tomographic fusion imaging in the diagnosis of avascular disease of the femoral head in adults. METHODS: Eighty-two adult patients with avascular necrosis of the femoral head confirmed by MRI in the department of orthopedics of our hospital were studied retrospectively. The related signs of adult avascular necrosis of the femoral head were diagnosed by digital tomographic fusion imaging, and the detection rates of digital X-ray (DR) and digital tomosynthesis (DTS) were compared to clarify the clinical value of digital tomographic fusion imaging in the diagnosis of adult avascular necrosis of the femoral head. RESULTS: DTS detected DR and 78 cases identified 55 cases. Taking the results of CT/MRI as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of DR and DTS in the diagnosis of ANFH were calculated. There was a significant difference in the detection rate between the two methods (P < 0.05). CONCLUSION: The digital tomographic fusion imaging technique has the advantages of high detection rate and excellent image quality, is economical, and is worth popularizing. For those with negative X-rays, DTS diagnosis and CT or/and MRI can avoid unnecessary CT and MRI examinations, which is helpful to reduce the waste of medical resources.

Noncoding RNAs in doxorubicin-induced cardiotoxicity and their potential as biomarkers and therapeutic targets.

Anthracyclines, such as doxorubicin (DOX), are well known for their high efficacy in treating multiple cancers, but their clinical usage is limited due to their potential to induce fatal cardiotoxicity. Such detrimental effects significantly impact the overall physical condition or even induce the morbidity and mortality of cancer survivors. Therefore, it is extremely important to understand the mechanisms of DOX-induced cardiotoxicity to develop methods for the early detection of cytotoxicity and therapeutic applications. Studies have shown that many molecular events are involved in DOX-induced cardiotoxicity. However, the precise mechanisms are still not completely understood. Recently, noncoding RNAs (ncRNAs) have been extensively studied in a diverse range of regulatory roles in cellular physiological and pathological processes. With respect to their roles in DOX-induced cardiotoxicity, microRNAs (miRNAs) are the most widely studied, and studies have focused on the regulatory roles of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), which have been shown to have significant functions in the cardiovascular system. Recent discoveries on the roles of ncRNAs in DOX-induced cardiotoxicity have prompted extensive interest in exploring candidate ncRNAs for utilization as potential therapeutic targets and/or diagnostic biomarkers. This review presents the frontier studies on the roles of ncRNAs in DOX-induced cardiotoxicity, addresses the possibility and prospects of using ncRNAs as diagnostic biomarkers or therapeutic targets, and discusses the possible reasons for related discrepancies and limitations of their use.