Cascade catalysis-coordinated nanorobots toward synergistic cancer chemoimmunotherapy.

Cancer has always been the biggest threat to human health, but the effect of traditional treatments such as surgery, chemotherapy, and radiotherapy is not satisfactory. Currently, nanomedicine-based chemoimmunotherapy can improve clinical results through unique synergistic effects. However, it is mainly enriched at tumor sites based on EPR effects, without an active delivery strategy and relatively low tumor targeting distribution. Therefore, nanorobots (Cu@MPS-GOD) with magnetic responsiveness and enzyme-like activity were prepared, which can enrich and move to the tumor site under the action of a 3D magnetic field, and cause tumor cell immunogenic death by cascade catalytic Fenton reactions. Meanwhile, Cu@MPS-GOD can also activate immune cells or induce cancer cells to expose surface antigens, trigger systemic anti-cancer immunity, and have a good inhibitory effect on a breast tumor model in mice with an inhibition rate of 59.3%. This work provides an attractive strategy to expand the therapeutic effect of cancer when chemical dynamic therapy is combined with immunotherapy, which has a potential clinical application prospect.

An analysis of the nutritional effects of Schisandra chinensis components based on mass spectrometry technology.

Objective: Schisandra chinensis (Turcz.) Baill. (S. chinensis) is a Traditional Chinese medicinal herb that can be used both for medicinal purposes and as a food ingredient due to its beneficial properties, and it is enriched with a wide of natural plant nutrients, including flavonoids, phenolic acids, anthocyanins, lignans, triterpenes, organic acids, and sugars. At present, there is lack of comprehensive study or systemic characterization of nutritional and active ingredients of S. chinensis using innovative mass spectrometry techniques. Methods: The comprehensive review was conducted by searching the PubMed databases for relevant literature of various mass spectrometry techniques employed in the analysis of nutritional components in S. chinensis, as well as their main nutritional effects. The literature search covered the past 5 years until March 15, 2023. Results: The potential nutritional effects of S. chinensis are discussed, including its ability to enhance immunity, function as an antioxidant, anti-allergen, antidepressant, and anti-anxiety agent, as well as its ability to act as a sedative-hypnotic and improve memory, cognitive function, and metabolic imbalances. Meanwhile, the use of advanced mass spectrometry detection technologies have the potential to enable the discovery of new nutritional components of S. chinensis, and to verify the effects of different extraction methods on these components. The contents of anthocyanins, lignans, organic acids, and polysaccharides, the main nutritional components in S. chinensis, are also closely associated to its quality. Conclusion: This review will provide guidelines for an in-depth study on the nutritional value of S. chinensis and for the development of healthy food products with effective components.

Intelligent Jellyfish-type Janus Nanoreactor Targeting Synergistic Treatment of Bacterial Infections.

Infections caused by multidrug-resistant bacteria continue to pose a serious threat to human health, and therefore it is important to explore the availability of antimicrobial drugs and modalities. Herein, jellyfish-type irregular mesoporous iron oxide nanoreactors containing ciprofloxacin, Janus Fe3O4@mSiO2@Cip nanoparticles (JFmS@Cip NPs), were developed for pH-responsive synergistic antimicrobial therapy in a microacidic environment. Compared with the use of symmetric nanocarriers, the asymmetric decoration on both sides of the particles allows different components to act on bacteria, Fe3O4 NPs have good magnetic and peroxidase-like catalytic activity, and the antibiotic ciprofloxacin can kill bacteria efficiently. Notably, due to the synergistic effect between different components of Janus particles, in vitro antibacterial experiments showed that JFmS@Cip NPs can kill bacteria efficiently at low concentrations, reaching an antibacterial rate of 99.6%. JFmS@Cip NPs combine multiple antibacterial properties that can be used to improve the therapeutic efficacy of current nanomedicines against drug-resistant bacteria.

Extract of Corallodiscus flabellata attenuates renal fibrosis in SAMP8 mice via the Wnt/ß-catenin/RAS signaling pathway.

BACKGROUND: Fibrosis is one of the most common pathological features of the aging process of the kidney, and fibrosis in aging kidneys also aggravates the process of chronic kidney disease (CKD). Corallodiscus flabellata B. L. Burtt (C. flabellata, CF) is a commonly used botanical drug in Chinese folklore. However, few studies have reported its pharmacological effects. This study aimed to explore the effect of CF ethanol extract on renal fibrosis in SAMP8 mice and identify potentially active compounds. METHODS: Senescence-accelerated mouse-prone 8 (SAMP8) were used as animal models, and different doses of CF were given by gavage for one month. To observe the degree of renal aging in mice using ß-galactosidase staining. Masson staining and the expression levels of Col-I, α-SMA, and FN were used to evaluate the renal fibrosis in mice. The protein expression levels of Nrf2 pathway and Wnt/ß-catenin/RAS pathway in the kidney were measured. And ß-galactosidase (ß-gal) induced NRK-52E cells as an in vitro model to screen the active components of CF. RESULTS: The CF ethanol extract significantly inhibited the activity of renal ß-galactosidase and the expression levels of Col-I, α-SMA, and FN in SAMP8 mice, and improved Masson staining in SAMP8 mice. CF remarkably reduced urinary protein, creatinine, urea nitrogen and serum levels of TNF-α and IL-1ß in SAMP8 mice, and significantly increased the levels of SOD and GSH-Px. Moreover, CF activated the Nrf2 pathway and blocked the Wnt/ß-catenin/RAS pathway in the kidneys of mice. Besides, 3,4-dihydroxyphenylethanol (SDC-0-14, 16) and (3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-ß-D-apiofuranosyl-(1→3)-ß-D-glucopyranosyl (1→6)]-ß-D-glucopyranoside (SDC-1-8) were isolated from CF, which reduced the senescence of NRK-52E cells, and maybe the active ingredients of CF playing the anti-aging role. CONCLUSIONS: Our experiments illuminated that CF ethanol extract may ameliorate renal fibrosis in SAMP8 mice via the Wnt/ß-catenin/RAS pathway. And SDC-0-14,16 and SDC-1-8 may be the material basis for CF to exert anti-renal senescence-related effects.

Oleic acid alleviates LPS-induced acute kidney injury by restraining inflammation and oxidative stress via the Ras/MAPKs/PPAR-γ signaling pathway.

BACKGROUND: Rehmannia Glutinosa Libosch. is applied for the treatment of renal and inflammatory-related diseases, and oleic acid (OA) is a compound isolated from Rehmannia Glutinosa Libosch.. Unfortunately, the pharmacological activity of OA on LPS treated acute kidney injury (AKI) has not been investigated. AIMS: The research is aiming to probe the activities of OA on LPS-induced AKI. METHODS: Information of OA effect on AKI were from network pharmacology. H&E staining, creatinine (CRE) and urea nitrogen (UN) were performed to evaluate the activities of OA on kidney function. Inflammatory factors in serum were measured by cytometric bead array. Increased ratio of reactive oxygen species (ROS) in kidney and immune cells in the peripheral blood were determined by flow cytometry (FCM). PPAR-γ, MAPK and apoptotic signaling pathways were measured by Western blot. Then, a metabolomics approach was utilized to investigate OA's response to AKI. The role of salirasib (FTS, Ras inhibitor) in OA acted on ROS, Ca2+, MMP and Ras signaling pathway in LPS treated NRK-52e cells were investigated by FCM and In-cell western. RESULTS: It is proved that OA effetively ameliorated renal function, alleviated inflammatory response and oxidative stress, and transformed apoptotic, MAPK and PPAR-γ signaling pathways in mice with AKI, regulated phenylalanine metabolism, purine metabolism, sphingolipid metabolism, taurine and hypotaurine metabolism, moreover, the role of OA in injury of NRK-52e was blocked by FTS. CONCLUSION: In a word, OA could alleviate AKI by restraining inflammation and oxidative stress via regulating the Ras/MAPKs/PPAR-γ signaling pathway, phenylalanine metabolism, purine metabolism, sphingolipid metabolism and taurine and hypotaurine metabolism, which might be a useful strategy for treating AKI.

The impact of recent chemotherapy on immunity in 2 COVID-19 cases with gastrointestinal tumors: A case report.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a rapidly emerging infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2. Currently, more than 100 million cases of COVID-19 have been confirmed worldwide, with over 2.4 million mortalities. The pandemic affects people of all ages but older individuals and those with severe chronic illnesses, including cancer patients, are at higher risk. PATIENT CONCERNS: The impact of cancer treatment on the progression of COVID-19 is unclear. Therefore, we assessed the effects of chemotherapy on COVID-19 outcomes for 2 cancer patients. On January 24, 2020, a level I response to a major public health emergency was initiated in Hubei Province, China, which includes Enshi Autonomous Prefecture that has a population of 4.026 million people. As of April 30, 2020, 252 confirmed cases of COVID-19 and 11 asymptomatic carriers were identified in Enshi. DIAGNOSIS: Among the confirmed cases and asymptomatic carriers, 2 patients were identified who were previously diagnosed with malignant tumors, including one with hepatocellular carcinoma and the other with cardia carcinoma. INTERVENTIONS: These 2 patients were receiving or just completed chemotherapy at the time of their COVID-19 diagnosis. OUTCOMES: Both patients were followed and presented favorable outcomes. The positive outcomes for these 2 patients could be partially explained by their recent chemotherapy that impacted their immune status. Also, their relatively younger ages and lack of comorbidities were likely factors in their successful recovery from COVID-19. CONCLUSIONS: Anticancer treatment might enhance a patient's ability to respond favorably to COVID-19 infection. However, anticancer treatment is likely to impact immune function differently in different individuals, which can influence disease outcomes.

Arbutin attenuates LPS-induced acute kidney injury by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway.

BACKGROUND: Arbutin (Ar) has anti-oxidative and anti-inflammatory activities. However, the effects of Ar on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) are not clear. PURPOSE: This study aimed to investigate the effects of Ar on LPS-induced AKI in rats. METHODS: The possible data regarding the effects of Ar on AKI were collected by network pharmacology research. Histological changes in the kidney and the levels of blood urea nitrogen, serum creatinine, and kidney injury molecule 1 were measured to assess the effects of Ar on renal function in LPS-induced AKI. The levels of inflammatory were detected by live small-animal imaging, cytometric bead array and enzyme linked immunosorbent assay. The levels of reactive oxygen species and apoptosis of primary kidney cells were detected by flow cytometry. The oxidative stress-related markers were detected by the cuvette assay. The TLR4/NF-κB and PI3K/Akt/Nrf2 levels and apoptosis were detected by Western blot analysis. The effects of GDC-0068 (GDC, Akt inhibitor) on Ar interposed on LPS-induced NRK-52e cell apoptosis were investigated by flow cytometry. RESULTS: The data collected by network pharmacology suggested that Ar might inhibit AKI by exerting an anti-inflammatory effect and regulating the Akt signaling pathway. The experimental results showed that Ar markedly improved renal function, and attenuated inflammation and cell apoptosis via regulating PI3K/Akt/Nrf2 pathway following LPS challenge in vivo, which blocked by GDC effectively in vitro. CONCLUSION: In a word, this study demonstrated that Ar attenuated LPS-induced AKI by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway.

Effect of roasting degree of coffee beans on sensory evaluation: Research from the perspective of major chemical ingredients.

As the most consumed beverage in the world, the material basis of the sensory quality for roasted coffee beans has always received much attention. The objective of the present study was to clarify the physical morphology changes, main chemical ingredients and cupping scores of arabica coffee beans of different roasting degrees, by scanning electron microscopy (SEM), nuclear magnetic resonance (NMR) and sensory analysis, respectively. Statistical analysis of the data by multivariate analysis demonstrated that trigonelline, sugars, malate, quinic acids, γ-butyro-lactone and acetate have the potential to be new roasting markers. Additionally, in all the sensory indicators, body and acidity were found to be susceptible to roasting degree. Basing on cluster heatmap and sensory molecular network, the complex relationships between sensory indicators and ingredients were discussed. The results of partial least squares regression (PLSR) showed that the content of the main coffee ingredients can be used to predict the body score.

Lactam ent-Kaurane Diterpene: A New Class of Diterpenoids Present in Roasted Beans of Coffea arabica.

Seven new lactam ent-kaurane diterpenoids, cafemides A-G (1-7), were isolated from roasted beans of Coffea arabica. Their structures were elucidated by extensive spectroscopic analysis including 1D, 2D NMR (heteronuclear single quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), 1H-1H correlation spectroscopy (COSY), and rotating frame Overhauser effect spectroscopy (ROESY)), high-resolution electrospray ionization mass spectrometry (HRESIMS), and IR spectra. They were divided into subtype I-III according to the structure. Further, with the aid of liquid chromatography-tandem mass spectrometry (LC-MS/MS) based molecular network, seven (8-14) subtype II diterpenoids were successfully identified. In addition, a variety of other subtypes of N-containing diterpenoids have been proven in roasted coffee. Compounds 1, 2, 3, 5, and 7 showed a moderate inhibitory effect on α-glucosidase with an IC50 value of 8.28 ± 0.62 µM, 38.23 ± 8.87 µM, 28.94 ± 1.42 µM, 12.44 ± 1.37 µM, and 22.2 ± 5.34 µM, respectively. To the best of our knowledge, this is the first time that N-containing diterpenoids have been reported in coffee.

Structurally diverse lanostane triterpenoids from medicinal and edible mushroom Ganoderma resinaceum Boud.

Ganoderma resinaceum is a multi-purpose herbal medicine that is homologous to functional food that has long been used for enhancing health and treating chronic hepatopathy in Traditional Chinese Medicine. In a search program to discover the key bioactive composition of G. resinaceum, sixteen new lanostane-type triterpenoids (1-16), and twenty known analogues (17-36) were isolated from the fruiting bodies of G. resinaceum. Spectroscopic analyses and X-ray crystallography were used to determine the new structures. Furthermore, the spectroscopic properties of 15ß-hydroxy-4,4,14α- trimethyl-3,7,11,20-tetraoxo-5α-pregn-8-ene (15) and 15α-hydroxy-4,4,14α-trimethyl- 3,7,11,20-tetraoxo-5α-pregn-8-ene (34) indicated a potential structural misassignment of their analogues, lucidone E and lucidone H, reported previously. To probe this hypothesis, ROESY experiments and single-crystal X-ray diffraction analysis were conducted. These results undoubtedly reassigned the structure of lucidone E and lucidone H. Biological evaluation of the selected compounds disclosed that compounds 3, 4, 7/21, 11, 12, 13/14, 17, 18, 24/25, 27, 30, 31, and 35 had significant hepatoprotective activities, due to their remarkable in vitro inhibitory activities against the increase of ALT and AST levels in HepG2 cells induced by H2O2.

NMR-based Structural Classification, Identification, and Quantification of Triterpenoids from Edible Mushroom Ganoderma resinaceum.

Ganoderma mushrooms have been widely used as functional food in China, Japan, and Korea. Ganoderma triterpenoids are deemed to be the main functional constituents. The structures of Ganoderma triterpenoids are complex but quite similar, which makes their analyses markedly limited. In this study, we developed a general 2D NMR method to differentiate Ganoderma triterpenoids, which classifies them into six types (A-F). Then, by the NMR-based isolation of A-F type triterpenoids from the fruiting bodies of G. resinaceum, four new compounds (1-4) and eight known compounds (5-12) were obtained. Moreover, combined with spiking experiments in 1D and 2D NMR spectra, compounds 5, 7, and 8, which belong to triterpenoids of A and B types, were identified. At the end, to achieve a more extensive application for this NMR method, a qNMR method for the absolute quantification of 5, 7, and 8 in the gross triterpenoids from G. resinaceum was set up. The results showed that this NMR method is reliable for the NMR-guided isolation and quantification of triterpenoids in G. resinaceum.

Lanostane triterpenoids with anti-inflammatory activities from Ganoderma lucidum.

Ganoderma lucidum is one of the most famous medicinal fungi and is traditional Chinese medicine with various biological activities in Asian countries. To clarify its pharmacodynamic material basis, 15 lanostane triterpenoidswere obtained from the fruiting bodies of G. lucidum, including 8 previously undescribed lanostanoids. Their structures, including absolute configuration, were established based on ultraviolet, infrared, high-resolution electrospray ionisation mass spectrometry, 1D and 2D nuclear magnetic resonance, and X-ray crystallographic analysis. Ganoluciduone A was an unusual octonorlanostane, which was isolated from Ganoderma for the first time. In addition, the anti-inflammatory activities of all isolates were evaluated by observing their inhibitory effects on nitric oxide production in RAW264.7 cells activated by a lipopolysaccharide. Ganoluciduone B exhibited moderate inhibitory activity on nitric oxide production, with an inhibition rate of 45.5% at a concentration of 12.5 µM.

C30 and C31 Triterpenoids and Triterpene Sugar Esters with Cytotoxic Activities from Edible Mushroom Fomitopsis pinicola (Sw. Ex Fr.) Krast.

Fomitopsis pinicola (Sw. Ex Fr.) Krast has been commonly used as a health food source and antitumor agent. To uncover bioactive key composition of F. pinicola, in our study, we investigated the chemical constituents of a methanol extract of F. pinicola and thirty-five lanostane-type tritetpenoids; 13 new compounds (1-13) and twenty-two known analogues (14-35) were isolated. Among them, compounds 1-9 were C30 lanostane triterpenoids and triterpene sugar esters, while compounds 10-13 were C31 triterpenoids and triterpene sugar esters. Their structures and absolute configurations were elucidated by extensive 1D, 2D NMR, MS, and IR spectra. Furthermore, cytotoxic activities of all isolates against five human tumor cell lines (HL-60, A549, SMMC-7721, MCF-7, and SW480) were evaluated. The results showed that compounds 12, 14, 17, 18, 22, and 23 displayed cytotoxic effects against five human tumor cell lines with IC50 values ranging from 3.92-28.51 µM. Meanwhile, compounds 9 and 35 exhibited selected inhibitory activities against HL-60, SMMC-7721, and MCF-7 with IC50 values in the range of 13.57-36.01 µM. Furthermore, the flow cytometry analysis revealed that compounds 17, 22, and 35 induced apoptosis in HL-60 cell lines. Their structure-activity relationships were preliminarily reported. These findings indicate the vital role of triterpenoids and their glycosides in explaining antitumor effects of F. pinicola and provide important evidence for further development and utilization of this fungus.

Effect of bamboo vinegar powder as an antibiotic alternative on the digesta bacteria communities of finishing pigs.

This study investigated the use for bamboo vinegar powder as an antibiotic alternative in the diet of growing-finishing pigs by examining their digestive bacterial communities. Forty-five Duroc × Landrace × Yorkshire growing-finishing pigs were randomly allocated to five diet groups: 0%, 0.5%, 1.0%, or 1.5% bamboo vinegar levels and antibiotics. After 37 days, the digesta in duodenum of four pigs from each treatment were analyzed for their bacterial community compositions using 16S rRNA gene sequencing. The addition of 1.5% bamboo vinegar powder had an effect on the intestinal microflora most similar to that of antibiotics, indicating its potential to promote the growth and development of finishing pigs. We also found the 1.5% bamboo vinegar powder group to have an increased abundance of Firmicutes/Bacteroidetes compared with the other bamboo vinegar powder groups, which may enhance the ability of the host to absorb food energy and store more body fat. Additionally, the effects of bamboo vinegar powder on promoting the abundances of Lactobacillus and Thalassospira and on inhibiting Streptococcus and Prevotella growth revealed it may play an important role in animal production. Moreover, functional predictions of microbes via PICRUSt indicated that feed supplemented with 1.5% bamboo vinegar powder could promote many vital metabolic pathways.

Antibacterial activity of Artemisia asiatica essential oil against some common respiratory infection causing bacterial strains and its mechanism of action in Haemophilus influenzae.

The main objective of the current study was to investigate the chemical composition of the essential oil of Artemisia asiatica together with investigating the antibacterial effects it exerts on several common respiratory infection causing bacteria including Haemophilus influenzae. Its mechanism of action was studied using various state-of-the-art assays like scanning electron microscopy, DNA, RNA and protein leakage assays, growth curve assays etc. The essential oil was extracted from the leaves of A. asiatica by supercritical CO2 fluid extraction technology. Chemical composition of essential oils was analyzed by gas chromatography-mass-spectrometry (GC-MS). The antibacterial activity was evaluated against 6 bacteria by the paper disc diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericide concentration (MBC) values of the essential oil were estimated by agar dilution method. The antibacterial mechanism was evaluated by growth curve, the integrity of cell membrane and scanning electronmicroscope (SEM). Gas chromatographic analysis of the A. asiatica essential oil led to the identification of 16 chemical constituents accounting for 97.2% of the total oil composition. The major components were found to be Piperitone, (z)-davanone, p-cymene and 1, 8-cineole. The essential oil showed maximum growth inhibition against Haemophilus influenzae with a zone of inhibition of 24.5 mm and MIC/MBC values of 1.9/4.5 mg/mL respectively. Bacteria treated with the essential oil led to a rapid decrease in the number of viable cells. On adding the essential oil of A. asiatica to the bacterial culture, the constituents of the bacterial cell got released into the medium and this cell constituent release increased with increasing doses of the essential oil. SEM showed that the bacterial cells treated with the essential oil showed damaged cell wall, deformed cell morphology and shrunken cells.

Two New Flavonol Glycosides from Polygala sibirica L. var megalopha Fr.

Two new flavonol glycosides, named polygalin H (1) and polygalin I (2), as well as the known compound polygalin D (3), were isolated from the whole plant of Polygala sibirica L. var megalopha Fr. Their structures were elucidated on the basis of spectroscopic data analysis. These flavonol glycosides exhibited strong inhibitory activities against xanthine oxidase in vitro. Their half-maximal inhibitory concentrations (IC50) were calculated, which were 9.48, 8.31, 16.00 µM, respectively.

Surveillance of antimicrobial susceptibilities of Neisseria gonorrhoeae in Nanning, China, 2000 to 2012.

OBJECTIVES: To monitor the frequency of antibiotic resistance of Neisseria gonorrhoeae (NG) in Nanning, China, between 2000 and 2012. METHODS: The production of ß-lactamase by NG isolates was determined using the paper acidometric testing method. Antimicrobial susceptibility testing was performed for tetracycline, ciprofloxacin, spectinomycin, and ceftriaxone using the agar dilution method. The χ(2) test, t test, and univariate and multivariate analyses were used to analyze the statistical difference of the results. RESULTS: A total of 923 NG isolates were collected in Nanning between 2000 and 2012. Among these, 131 (14.2%) were penicillinase-producing NG, 520 (56.3%) isolates were tetracycline-resistant NG, and 857 (92.9%) isolates were ciprofloxacin-resistant strains. One spectinomycin-resistant strain was identified in 2000. There were 304 (32.9%) isolates with decreased susceptibility to ceftriaxone; the proportion of such isolates increased from 22.8% in 2000 to 2002 to 48.9% in 2006 to 2008 (P < 0.001), followed by a fall to 32.2% in 2009 to 2012 (P = 0.001). Patients' age of 16 to 25 years and isolate collection period of 2008 to 2012 (except 2011) were demonstrated to be risk factors for infection with isolates with decreased susceptibility to ceftriaxone. CONCLUSIONS: Antimicrobial susceptibility of NG isolates obtained from patients in Nanning from 2000 to 2012 was characterized by high occurrence of penicillinase-producing NG, tetracycline-resistant NG, and ciprofloxacin-resistant strains. Spectinomycin and ceftriaxone can be considered drugs of choice for empirical treatment of NG infection in Nanning. Moreover, we recommend a combination of 500 mg or higher dose of intramuscular ceftriaxone and 1 g oral azithromycin be used for the treatment of NG infection in Nanning and possibly in China.