ABSTRACT
Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.
ABSTRACT
OBJECTIVE： To investigate the effects of different polar parts of 5 kinds of Alpinia on the function of sympathetic-adrenal system in gastric ulcer model rats with cold syndrome， such as the root of Alpinia officinarum， the rhizome and fruit of Alpinia galangal， the seed of Alpinia katsumadai， and the fruit of Alpinia oxyphylla. METHODS： SD rats were given Anemarrhena asphodeloides decoction at 4 ℃ and Glacial acetic acid solution intragastrically to induce gastric ulcer model with cold syndrome； the model rats were randomly divided into model group， Fuzi lizhong pills group （positive control， 9.0 g/kg）， cimetidine group （positive control， 0.003 3 g/kg）， low-dose and high-dose groups of petroleum ether， ethyl acetate， n-butanol and water extraction parts from 5 medicinal materials （hereinafter referred to as “gaoshidi” “gaoshigao” “dashidi” “dashigao” “hongshidi” “hongshigao” “caoshidi” “caoshigao” “yishidi” “yishigao” “gaoyidi” “gaoyigao” “dayidi” “dayigao” “hongyidi” “hongyigao” “caoyidi” “caoyigao” “yiyidi” “yiyigao” “gaozhengdi” “gaozhenggao” “dazhengdi” “dazhenggao” “hongzhengdi” “hongzhenggao” “caozhengdi” “caozhenggao” “yizhengdi” “yizhenggao” “gaoshuidi” “gaoshuigao” “dashuidi” “dashuigao” “hongshuidi” “hongshuigao” “caoshuidi” “caoshuigao” “yishuidi” “yishuigao”， 0.064/0.256， 0.032/ 0.128， 0.008/0.032， 0.075/0.3， 0.1/0.4， 0.064/0.256， 0.108/0.432， 0.16/0.64， 0.064/0.25， 0.125/0.5， 0.056/0.224， 0.108/0.432， 0.08/0.32， 0.2/0.8， 0.3/1.2， 0.14/0.56， 0.032/0.128， 0.028/0.112， 0.05/0.2， 0.087/0.348 g/kg， by mass of extraction parts）， with 10 rats in each group； and the blank group （normal temperature water） was set up. Next day after modeling， blank group and model group were given constant volume of normal temperature water intragastrically； administration group was given relevant solution 2 mL/100 g intragastrically， q12 h， 4 times in total. After last medication， urine contents of 17-OHCS， CAs substances （A， NE， DA） and serum contents of ACTH and D-β-H were determined by ELISA. RESULTS： Compared with blank group， the contents of 17-OHCS， A， NE and DA in urine， the contents of ACTH and D-β-H in serum were decreased significantly in model group （P＜0.01）. Compared with model group， the contents of 17-OHCS （Fuzi lizhong pills group， cimetidine group， gaoshidi， gaoshigao， dashigao， hongshigao， caoshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials， dazhenggao， hongzhenggao， caozhenggao and yizhenggao groups， gaoshuigao， dashuigao and hongshuigao groups）， A （Fuzi lizhong pills group， cimetidine group， gaoshigao， dashigao， hongshidi， hongshigao， caoshidi， caoshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials， gaozhenggao， dazhenggao， hongzhengdi， hongzhenggao， caozhenggao and yizhenggao groups， hongshuigao group）， NE （Fuzi lizhong pills group， cimetidine group， petroleum ether part， ethyl acetate part and n-butanol part groups of 5 medicinal materials， gaoshuigao， dashuigao and hongshuigao groups）， DA [Fuzi lizhong pills group， cimetidine group， petroleum ether part （except for gaoshidi group） and ethyl acetate part groups of 5 medicinal materials， gaozhenggao， dazhenggao， hongzhenggao， caozhenggao and yizhenggao groups， hongshuigao group] in urine， serum contents of ACTH [Fuzi lizhong pills group， petroleum ether part （except for gaoshidi， dashidi and caoshidi groups） and ethyl acetate part （except for dayidi and hongyidi groups） groups of 5 medicinal materials， hongzhenggao group， dashuigao group]， and D-β-H [Fuzi lizhong pills group， gaoshigao， dashigao， hongshidi， hongshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials （except for dayidi， hongyidi and yiyidi groups）， dazhenggao and hongzhenggao groups， hongshuigao group] were increased significantly （P＜0.05 or P＜0.01）. The contents of 17-OHCS and D-β-H in dashigao group， the contents of ACTH and D-β-H in caoshigao group and the contents of D-β-H in gaoshigao and yishigao groups were significantly lower than hongshigao group. The contents of DA in gaoyigao， caoyigao and yiyigao groups as well as the contents of D-β-H in gaoyigao， hongyigao， caoyigao and yiyigao groups were significantly lower than dayigao group； the contents of DA in gaoyigao and caoyigao groups were significantly lower than hongyigao group， the contents of ACTH in gaoyigao， dayigao， caoyigao and yiyigao groups were significantly higher than hongyigao group. The contents of 17-OHCS， DA and ACTH in gaozhenggao， dazhenggao， caozhenggao and yizhenggao groups， the contents of A in dazhenggao， caozhenggao and yizhenggao groups as well as the contents of D-β-H in gaozhenggao， caozhenggao and yizhenggao groups were significantly lower than hongzhenggao group. The contents of 17-OHCS and D-β-H in caoshuigao and yishuigao groups were significantly lower than dashuigao group. The contents of 17-OHCS， DA and D-β-H in caoshuigao and yishuigao groups as well as the contents of DA and D-β-H in gaoshuigao groups were significantly lower than hongshuigao group （P＜0.05 or P＜0.01）. CONCLUSIONS： Different polar parts of 5 kinds of Alpinia can improve gastric ulcer model rats with cold syndrome to different extents； among them， the fruit of A. galangal is the best， followed by the root of A. officinarum. Above medicinal materials can regulate the function of sympathetic-adrenal system by increasing the contents of 17-OHCS， CAs and D-β-H.
ABSTRACT
Objective To investigate the relationship between serum markers β amyloid (Aβ), tau and thyroid hormone levels and post-stroke cognitive impairment (PSCI) in the acute phase of cerebral infarction. Methods A total of 214 patients with acute cerebral infarction were enrolled. The baseline data and serological indicators were collected and the cognitive function of patients was evaluated. All patients were divided into cognitive impairment group and normal group based on follow-up results. The differences of Aβ1-42, tau protein and thyroxine levels between the two groups and their relationship with disease progression were analyzed. The Cox regression analysis and ROC curve were used to compare the above parameters to predict the development of PSCI. Results The total protein level of Tau (210.6 ±98.9 pg/mL) was higher and Aβ1-42 (426.1 ±123.5 pg/mL) and triiodothyronine (T3) (1.43 ±0.57 nmol/L), free thyroxine (FT4) (13.15±2.23 pmol/L) was significantly lower in the cognitive impairment group than in the normal group (P<0.05). Tau protein (r=-0.457), Aβ1-42 (r=0.348), T3 (r=0.211), and FT4 (r=0.306) were all associated with disease progression (P<0.05). Cox regression analysis showed that Aβ1-42 and T3 were important influencing factors in the occurrence of PSCI. The area under the curve of Aβ1-42 combined with T3 was 0.841. The specificity and the sensitivity were 74.8% and 85.3%, respectively, with a diagnostic cutoff value of 0.572. Conclusion Aβ1-42 and T3 levels in the acute phase of cerebral infarction may predict the progression of PSCI.
ABSTRACT
In order to explore the correlation between the medicinal properties，efficacy and application in the same genetic relationship，explain the scientific connotation of the medicinal properties and effects of traditional Chinese medicines(TCM)，promote the academic development of the theory of traditional Chinese medicines，and provide reference for the research and development of the traditional Chinese medicines of a same genus. In this paper, a literature study of ancient and modern works of Chinese herbal medicine was conducted to investigate the correlation between the properties, meridians tropism, efficacy and application of Alpinia officinarum， A. katsumadai， Galangae Fructus and Alpinae Oxyphyllae Fructus, four kinds of Alpinia Chinese medicines．The results showed that the similar properties of these four kinds of Alpinia Chinese medicines included that they were acrid, warm,and mainly getting into the spleen and stomach channels; the similar efficacies included that dispelling cold，relieving pain，warming stomach，anti-nausea，anti-diarrheal，reinforcing spleen to promote digestion and other effects; in application aspects, the similarities were that they were all mainly used in treatment of catching cold or spleen deficiency induced by abdominal pain，vomiting，diarrhea,diet indigestion, etc. indicating that phylogenetic relationship was closely related with the herbal properties, efficacy and application. It is an effective way to explore，collate and research traditional Chinese medicine by using plant phylogenetic relationships in exploring the internal relations and laws of TCM theories，material bases, pharmacological effects and clinical applications, also with a strong maneuverability to explain their scientific connotation.