Cancer nutritional-immunotherapy with NIR-II laser-controlled ATP release based on material repurposing strategy.

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.

The application of demographic characteristics of Ectropis grisescens (Lepidoptera: Geometridae) in pest risk assessment of IPM.

Ectropis grisescens Warren is one of the most important pests of tea plants. In this study, data on the development, survival, and fecundity of E. grisescens were collected at 15, 22, and 32 °C and analyzed by using the age-stage, two-sex life table. At 15 °C, the duration of the preadult period of E. grisescens was significantly prolonged (81.06 days), with high mortality (69.0%), and the proportion of emerged female adults was extremely low (7.0%). At 32 °C, the preadult period was significantly shortened (29.12 days), with high preadult mortality (74.0%), and a low proportion of emerged female adults (15.0%). At 22 °C, with low preadult mortality (24.0%), and a high proportion of emerged female adults (26.0%). The overall effects of the shorter preadult duration, higher preadult survival rate, higher proportion of emerged female adults, higher fecundity (F = 350.88 eggs/♀), and higher net reproductive rate (R0 = 91.23 offspring/individual) at 22 °C resulted in the highest values of the intrinsic rate of increase (r = 0.1054 days-1) and finite rate of increase (λ = 1.1112 days-1). Computer simulation showed that E. grisescens populations can increase much faster at 22 °C than at 15 and 32 °C. The weighted population size and cumulative weighted insect-days provided the dynamics necessary for estimating the damage potential of E. grisescens in devising economical pest management programs. Our results demonstrate that populations of E. grisescens were able to develop at a broad range of temperatures and adapt to the high temperatures. These finding can be utilized to improve the management of E. grisescens.

Acidity-Triggered Charge-Convertible Conjugated Polymer for Dihydroartemisinin Delivery and Tumor-Specific Chemo-Photothermal Therapy.

Since the nonspecificity and nonselectivity of traditional treatment models lead to the difficulty of cancer treatment, nanobased strategies are needed to fill in the gaps of current approaches. Herein, a tumor microenvironment (TME)-responsive chemo-photothermal treatment model was developed based on dihydroartemisinin (DHA)-loaded conjugated polymers (DHA@PLGA-PANI). The synthesized DHA@PLGA-PANI exhibited enhanced photothermal properties under mild-acidic conditions and thus triggered local heat at the tumor site. Meanwhile, these iron-doped conjugated polymers of PLGA-PANI were used as the source of Fe, and benefiting from the Fe-dependent cytotoxicity of DHA, the burst of free radicals could be generated in tumors. Therefore, the combination of TME-responsive chemo-photothermal therapy could achieve effective tumor efficacy.

[Meta-analysis and GRADE evaluation of Guanxinning Tablets in treatment of angina pectoris of coronary heart disease].

This study aims to evaluate the efficacy and safety of Guanxinning Tablets+conventional western medicine in the treatment of angina pectoris of coronary heart disease, and provide evidence-based references for clinical medication. Retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, randomized controlled trial(RCT) about Guanxinning Tablets for the treatment of angina pectoris of coronary heart disease from the inception to April 2022 were collected. After literature screening and data extraction, the bias risk assessment tool recommended by the Cochrane evaluation manual handbook 5.1.0 was used to evaluate the quality of the included literature, and RevMan 5.3 and Stata 14.0 were used for Meta-analysis. Eighteen RCTs were finally included, involving 2 281 patients. Meta-analysis showed that, compared with conventional western medicine treatment alone, Guanxinning Tablets+conventional western medicine significantly improved angina pectoris efficacy(RR=1.33, 95%CI[1.13, 1.57], P=0.000 8), electrocardiogram efficacy(RR=1.32, 95%CI[1.02, 1.71], P=0.03), and exercise duration(MD=59.53, 95%CI[39.16, 79.90], P<0.000 01) and reduced the incidence of cardiovascular events(MACE)(RR=0.43, 95%CI[0.30, 0.61], P<0.000 01), high sensitivity C-reactive protein(hs-CRP)(MD=-2.75, 95%CI[-3.71,-1.79], P<0.000 01), and endothelin-1(ET-1) levels(MD=-9.34, 95%CI[-11.36,-7.32], P<0.000 01). There was no statistically significant difference in the incidence of adverse reactions between two groups(RR=0.91, 95%CI[0.68, 1.22], P=0.52). Subgroup analysis showed that Guanxinning Tablets may have better short-term efficacy(less than 6 months) in the treatment of heart-blood stasis syndrome. GRADE grading showed that angina pectoris efficacy, electrocardiogram efficacy, MACE, and ET-1 were in the medium grade, hs-CRP and adverse reactions were in the low grade, and exercise duration was in the extremely low grade. In conclusion, the efficacy of Guanxinning Tablets+conventional western medicine is better than conventional western medicine treatment alone, with good safety. Therefore, it is recommended for the short-term treatment of patients with heart-blood stasis syndrome. However, the evidence quality of some results is low, and more rigo-rous RCT is still needed to enhance the reliability of evidence.

A rare case of pancytopenia causing- Sheehan's syndrome: Case report and literature review.

We describe the case of a 58-year-old woman who was presented with pancytopenia and hypofibrinogenemia. Treatment with iron supplementation was not satisfactory. Physical findings and a history of a massive postpartum hemorrhage suggested Sheehan's syndrome(SS). After thyroxine and glucocorticoid replacement therapy, the blood cell count improved. SS is a rare etiology of hemocytopenia, of which hematologists need to be aware. We conclude that hormonal therapy can produce full hematological recovery.

Hypoxia Alleviated and One Photo-Triggered Thermal/Dynamic Nanoplatform for Immunogenic Cell Death-Initiated Cancer Immunotherapy.

Immunogenic cell death (ICD) induced by treatment modalities like chemotherapy, radiotherapy, and photothermal and photodynamic therapy has shown great potential to improve the low response rate of various solid tumors in cancer immunotherapy. However, extensive studies have revealed that the efficacy of cancer treatment is limited by the hypoxia and immunosuppression in the tumor microenvironment (TME). To address these challenges, a hypoxia alleviated and one phototriggered thermal/dynamic nanoplatform based on MnO2@PDA/ICG-BSA (MPIB) is developed for oxygen (O2) self-supply enhanced cancer phototherapy (PT). First, MnO2 transfers intracellular overexpression H2O2 into O2 in the acidic TME through its catalase-like activity to improve the hypoxia and also provide O2 for the following photodynamic therapy. Then, under single NIR-808 nm light irradiation (called the "phototherapeutic window"), excellent photothermal and photodynamic performance of the MPIB is activated for combined PT. Finally, assisted with immune adjuvant cytosine-phospho-guanine, obvious ICD and systemic antitumor immunity was elicited in PT-treated mice and demonstrated significant growth inhibition on distant tumors. This MPIB-based nanoplatform highlights the promise to overcome the limitations of hypoxia and also challenges of immunosuppressive tumor microenvironments for improved cancer immunotherapy.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Anti-Inflammatory Effects of Neochlorogenic Acid Extract from Mulberry Leaf (Morus alba L.) Against LPS-Stimulated Inflammatory Response through Mediating the AMPK/Nrf2 Signaling Pathway in A549 Cells.

Neochlorogenic acid (nCGA) is a phenolic compound isolated from mulberry leaf (Morus alba L.), which possesses multiple pharmacological activities containing antioxidant and anti-inflammatory effects. However, the role of nCGA in the treatment of acute pneumonia and the underlying molecular mechanism are still unclear. Hence, the aim of study is to investigate the anti-inflammatory properties of nCGA on LPS-stimulated inflammation in A549 cells. In the present study, results reported that nCGA without cytotoxicity significantly reduced the production of TNF-α, IL-6, and NO, and further suppressed the proteins of iNOS, COX2, TNF-α, IL-6 expression. Furthermore, nCGA also inhibited NF-κB activation and blocked MAPKs signaling pathway phosphorylation. In addition, we found nCGA significantly increased the expression of HO-1 via activating the AMPK/Nrf2 signaling pathway to attenuate the inflammatory response, whereas this protective effect of nCGA was reversed by pre-treatment with compound C (C.C, an AMPK inhibitor). Therefore, all these results indicated that nCGA might act as a natural anti-inflammatory agent for the treatment of acute pneumonia.

Silibinin in vitro protects A549 cells from Staphylococcus aureus-mediated injury and in vivo alleviates the lung injury of staphylococcal pneumonia.

In this study, hemolysis, Western blot, and real-time RT-PCR assays were performed to evaluate silibinin's activity against S. aureus α-toxin secretion. In addition, live/dead cell staining and lactate dehydrogenase activity assays were introduced to examine the influence of silibinin on α-toxin-induced cell injury in human alveolar epithelial cells. Furthermore, we tested the influence of silibinin on S. aureus pneumonia in a mouse model. We show that silibinin inhibits the expression of α-toxin in a dose-dependent manner and alleviates α-toxin-induced lung cell injury. The IC50 of silibinin that inhibits the hemolytic activity of S. aureus was 14.33 µg/mL for strain 8325-4. Moreover, this compound provides effective protection on the lung injury of staphylococcal pneumonia.