Rotor-based image-guided therapy of glioblastoma.

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.

[Study on alleviating neuroinflammatory injury in ischemic stroke rats by electrical stimulation with scalp acupuncture based on IFN-γ mediated JAK/STAT1 signaling pathway].

OBJECTIVE: To explore the molecular mechanism of electrical stimulation with scalp acupuncture (ESA) in alleviating neuroinflammatory injury in ischemic stroke rats based on interferon γ (IFN-γ)-mediated Janus kinase/signal transduction and transcriptional activator 1 (JAK/STAT1) signaling pathway. METHODS: Fifty-six SD rats aged 7 weeks were randomly divided into normal, model, ESA and inhibitor groups, with 14 rats in each group. The middle cerebral artery embolization rat model was established by means of thread embolization. Rats in the inhibitor group were intraperitoneally injected with the inhibitor PJ34 (5 mg/mL, 25 mg/kg) once a day for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. The percentage of cerebral infarction volume was detected by TTC staining. The positive expressions of interleukin (IL)-6 and IL-10 in cerebral cortex were detected by immunohistochemistry. The protein expression levels of IFN-γ, JAK1, JAK2 and phosphorylated (p)-STAT1 in rats cerebral cortex were detected by Western blot. RESULTS: Compared with the normal group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were increased (P<0.01), while the expression level of IL-10 was decreased (P<0.01) in the model group. Compared with the model group, the neurological deficit score and neurobehavioral score after treatment were significantly decreased (P<0.01), the percentage of cerebral infarction volume was decreased (P<0.01), the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were decreased (P<0.01), while the expression level of IL-10 was increased (P<0.01) in the ESA and inhibitor groups. ESA was superior to inhibitors in improving neurological deficit score and down-regulating p-STAT1 expression (P<0.05, P<0.01), and was inferior to inhibitor in reducing the percentage of cerebral infarction volume as well as down-regulating IFN-γ and JAK1 (P<0.01, P<0.05). CONCLUSION: Down-regulating the expression of IFN-γ and inhibiting the activity of JAK/STAT1 signaling pathway may be one of the mechanisms by which ESA alleviates neuroinflammatory injury in ischemic stroke rats.

[Exploration of the diagnosis and treatment for benign prostatic hyperplasia with acupuncture based on jingjin theory].

Benign prostatic hyperplasia is caused by kidney deficiency and impaired qi transformation of the urinary bladder and is manifested by the stagnation of essence chamber. Based on jingjin (muscle region of meridian, sinew/fascia) theory and taking the visceral membrane as the principal, acupuncture is delivered at sinew/fascia to promote qi circulation, resolve stasis and open the orifice. Guided by CT, the needle is inserted at Zhongji (CV 3), the front-mu point of the urinary bladder, and then goes to the prostatic capsule, meaning "the disease of zang organ is treated by needling the front-mu point". In treatment of benign prostatic hyperplasia, this acupuncture therapy stimulates the different layers of fascia, by which, the defensive qi on the exterior is regulated and "essence orifice" in the interior is adjusted so that the urination can be promoted.

In vitro antioxidative activity of Fritillaria cirrhosa D. Don straw ethanolic extract and its effect on lipid, protein oxidation, and quality of Chinese-style sausage.

Fritillaria cirrhosa D. Don, which can be used for medicine and food, contains a variety of chemicals including polyphenols, alkaloids, terpenoid, and others that have beneficial biological properties like antihypertension, bacteriostasis, and anti-inflammatory. The ethanolic extract of Fritillaria straw was obtained for this study using ultrasonic-aided extraction, and the amounts of total phenols and total flavonoids were 26.56 ± 1.36 mg GAE/g dw and 18.75 ± 0.80 mg RE/g dw, respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry technology was utilized to identify 50 major chemicals in the Fritillaria straw extract (FSE). Meanwhile, the antioxidative activities of FSE were evaluated by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and Ferric reducing antioxidant power assays in vitro, which pointed out the antioxidative potential of FSE. Additionally, 0.1%, 0.5%, and 1% of FSE and 0.02% butylated hydroxyanisole (BHA) + butylated hydroxytoluene (BHT) (1:1) were separately added to Chinese-style sausage to study their effects on the lipid oxidation, protein oxidation, and quality of the sausage at different storage times. The study found that the effect of adding 1% FSE on carbonyl content, total volatile basic nitrogen, and TVC of sausage could achieve the effect of the 0.02% BHA + BHT (1:1) group on the 35th day, and the thiobarbituric acid reactive substances value and peroxide value of sausage were significantly lower than the control group. Therefore, as one of the candidates to replace synthetic antioxidants, the FSE can be used in the production of Chinese sausages, which has a positive effect on improving the product's quality and extending the shelf life. PRACTICAL APPLICATION: The antioxidative activities of 50 main compounds were identified after the ethanolic extraction of Fritillaria straw. This Fritillaria straw extract was added to Chinese sausage, effectively inhibiting the oxidation of lipids and proteins as well as the decomposition of proteins. Obviously, the Fritillaria straw extract, one of the choices to replace synthetic antioxidants, may be useful for future meat processing, because of its positive impact on the product's quality and shelf life.

Anti-tumour effect of Huangqin Decoction on colorectal cancer mice through microbial butyrate mediated PI3K/Akt pathway suppression.

Introduction. Huangqin Decoction (HQD), a Chinese herbal formula, is widely used for various diseases, including colorectal cancer (CRC).Hypothesis/Gap Statement. We proposed that microbial butyrate mediated PI3K/Akt pathway suppression might involve the anti-cancer effect of HQD.Aim. This study aimed to evaluate the potential mechanism of HQD against CRC.Methodology. An azoxymethane plus dextran sulphate sodium induced CRC mouse model was used, and the intestinal flora and faecal short-chain fatty acid changes were detected, respectively, after HQD administration with 16S rRNA sequencing and gas chromatography coupled with mass spectrometry. Disease activity index, colon length and levels of inflammatory cytokines were measured to evaluate the effect of HQD on intestinal inflammation. Tumour size, number and histopathology were assessed to reflect the impact of HQD on tumour burden. Apoptosis and PI3K/Akt pathway activity were measured by TUNEL staining and Western-blotting. In vitro, the effects of sodium butyrate (NaB) on the viability of CRC cell lines were detected by the Cell-counting Kit-8. The apoptotic cells were determined by TUNEL staining. Cell migration and invasion were assessed by wound healing assay and Transwell assay, respectively. Western-blotting and immunofluorescent staining were used to test the activity of PI3K/Akt pathway.Results. Animal study showed that HQD could improve the gut dysbiosis, increase the abundance of Clostridium and the level of faecal butyric acid. Then, we found that HQD could attenuate colitis, reduce tumour burden, promote cell apoptosis and suppress PI3K/Akt pathway activity in CRC mice. In vitro experiment revealed that NaB treatment could inhibit cell growth, migration and invasion in CRC cell lines. Additionally, NaB enhanced cellular apoptosis, and reduced phosphorylated PI3K and Akt expressions. Interestingly, addition of 740Y-P, an agonist of PI3K, reversed the NaB effects on CRC cells.Conclusion. Overall, in this study, we revealed that HQD could induce apoptosis through microbial butyrate mediated PI3K/Akt inhibition and perform anti-CRC activity.

By-Products of Zea mays L.: A Promising Source of Medicinal Properties with Phytochemistry and Pharmacological Activities: A Comprehensive Review.

Zea mays (Z. mays) is one of the main cereal crops in the world, and it's by-products have exhibited medicinal properties to explore. This article intends to review the chemical compositions and pharmacological activities of by-products of Z. mays (corn silks, roots, bract, stems, bran, and leaves) which support the therapeutic potential in the treatment of different diseases, with emphasis on the natural occurring compounds and detailed pharmacological developments. Based on this review, 231 natural compounds are presented. Among them, flavonoids, terpenes, phenylpropanoids, and alkaloids are the most frequently reported. The by-products of Z. mays possess diuretic effects, hepatoprotective, anti-diabetic, antioxidant, neuroprotective, anti-inflammatory, anti-cancer, plant protection activity, and other activities. This article reviewed the phytochemistry and pharmacological activities of Z. mays for comprehensive quality control and the safety and effectiveness to enhance future application.

Real-world treatment patterns and healthcare costs in patients with psoriasis taking systemic oral or biologic therapies.

BACKGROUND: Psoriasis is a chronic, immune-mediated, systemic inflammatory disorder associated with high costs. This study evaluated real-world treatment patterns and associated costs in patients in the United States with psoriasis initiating systemic oral or biologic treatments. METHODS: This retrospective cohort study used IBM® (now Merative™) MarketScan® Commercial and Medicare claims (1 January 2006-31 December 2019) to evaluate patterns of switching, discontinuation, and nonswitching in two cohorts of patients initiating oral or biologic systemic therapy. Total pre-switch and post-switch costs were reported per-patient per-month (PPPM). RESULTS: Each cohort was analyzed (oral, n = 11,993; biologic; n = 9753). Among the oral and biologic cohorts, 32% and 15% discontinued index and any systemic treatment within 1 year of initiation; 40% and 62% remained on index therapy; and 28% and 23% switched treatment, respectively. In the oral and biologic cohorts, total PPPM costs within 1 year of initiation for nonswitchers, patients who discontinued, and patients who switched were $2594, $1402, and $3956, respectively, and $5035, $3112, and $5833, respectively. CONCLUSION: This study identified lower persistence in the oral treatment cohort, higher costs associated with switching, and a need for safe and effective oral treatment options for patients with psoriasis to delay the switch to biologic therapy.

[Application characteristics of Qugu (CV 2) in ancient and modern literature].

To summarize and analyze the clinical application characteristics of Qugu (CV 2) in ancient and modern literature based on data mining technology. The Chinese Medical Code (the 5th edition) was taken as the retrieval source of ancient literature, while the CNKI, Wanfang, and VIP databases were taken as the retrieval source of modern literature. The indications of Qugu (CV 2) used alone or with compatible acupoints, compatible acupoints, acupuncture-moxibustion manipulation, etc., were systematically sorted out. As a result, a total of 140 articles of ancient literature were included. The common indications of Qugu (CV 2) used alone were urinary retention, profuse vaginal discharge and hernia. The common indications of Qugu (CV 2) used with compatible acupoints were profuse vaginal discharge, stranguria and hernia. Sixty-four acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, bladder meridian and liver meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Sanyinjiao (SP 6); five-shu points were the most used special acupoints, and moxibustion therapy was often used. A total of 73 modern articles were included. The common indications of Qugu (CV 2) used alone were urinary retention, erectile dysfunction and chronic prostatitis; the common indications of Qugu (CV 2) used with compatible scupoints were urinary retention, erectile dysfunction and prostatic hyperplasia. Thirty-six acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, kidney meridian and spleen meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Zusanli (ST 36); front-mu points were the most used special acupoints, and acupuncture therapy was often used. Qugu (CV 2) treats a wide range of diseases in ancient times, the distant treatment effectiveness of acupoints is emphasized; and it mainly treats local diseases in modern times, the nearby treatment effectiveness of acupoints is emphasized.

Core-satellite nanoreactors based on cationic photosensitizer modified hollow CuS nanocage for ROS diffusion enhanced phototherapy of hypoxic tumor.

Photodynamic therapy (PDT) efficiency is directly affected by the reactive oxygen species (ROS) generated by photosensitizers. However, ROSs' ultrashort life span and limited diffusion distance restrict the PDT efficiency. Therefore, it is important to control the delivery strategy of photosensitizers for PDT treatment. Herein, the core-satellite nanoreactors were fabricated with oxygen generation and ROS diffusion properties. The hollow CuS encapsulating horseradish peroxidase (HRP) was combined with the cationic photosensitizers (PEI-Ce6). The unique photosensitizers delivery strategy makes the nanoreactors achieve ROS diffusion-enhanced PDT effect. First, HRP in "core" (HRP@CuS) can decompose hydrogen peroxide (H2O2) to O2, increasing O2 levels on the surface of the nanoreactor. Second, the Ce6 molecules covalent-linked with PEI are uniformly dispersed on the surface of CuS as a "satellite", avoiding Ce6 aggregation and causing more Ce6 molecules be activated to produce more 1O2. Due to the Ce6 was on the surface of the CuS nanocages, the generated ROS may ensure a larger diffusion range. Meanwhile, the inherently CuS nanocages exhibit photothermal and photoacoustic (PA) effect. The photothermal effect further enhances the ROS diffusion. Under the guidance of PA imaging, nanoreactors exhibit highly efficient hypoxic tumor ablation via photodynamic and photothermal effect. Overall, the core-satellite nanoreactors provide an effective strategy for tumor therapy, further promoting the research of photosensitizers delivery.

Chromosome-Level Genome Assembly of Herpetospermum pedunculosum (Cucurbitaceae).

This study presents a chromosome-level reference genome assembly of a traditional Tibetan medicinal plant, Herpetospermum pedunculosum belonging to the Cucurbitaceae family. Following a combined PacBio high-fidelity sequencing and Hi-C analysis, a final H. pedunculosum genome assembly, 804.11 Mb in length was obtained, 90.45% of which was anchored into ten pseudochromosomes with a contig N50 of 24.39 Mb. In addition, 579.55 Mb repetitive sequences and 23,924 high-confidence protein-coding genes were annotated. Phylogenetic analysis revealed that H. pedunculosum was sister to a clade formed by cucumber, zucchini, and wax gourd. Further whole-genome duplication analysis revealed no recent polyploidization event in the H. pedunculosum genome. The high-quality H. pedunculosum genome presented here will be highly useful in investigating the molecular mechanisms underlying the biosynthesis of its active compounds and adaptation strategies to the extreme environment. It will also provide great insights into comparative genomic studies of Cucurbitaceae and flowering plants.