Elemental diet preventative effects for adverse events during chemotherapy in patients with esophageal cancer - A systematic review and meta-analysis.

The effectiveness of an elemental diet (ED) for preventing adverse events (AEs) during chemotherapy for patients with esophageal cancer (EC) remains unclear. The aim of this meta-analysis was to comprehensively assess the efficacy of ED for preventing AE in EC patients during chemotherapy. Medline (via PubMed), Embase, the Cochrane Library, and Web of Science were searched to retrieve prospective and randomized studies published before April 12, 2023. The odds ratio (OR) of each AE was calculated using Review Manger 5.4.1. The risk of bias was assessed, and a random effect model-based meta-analysis was used to analyze the available data. Four prospective and randomized studies involving 237 patients were identified after a systematic search. Regarding gastrointestinal toxicities, the findings indicated a trend toward a decrease in the risk of mucositis (OM) (OR = 0.54, 95 % CI: 0.25-1.14), constipation (OR = 0.87, 95 % CI: 0.49-1.53), and anorexia (OR = 0.99, 95 % CI: 0.32-3.05), as well as an increasing trend in the risk of diarrhea (OR = 1.48, 95 % CI: 0.79-2.79), among patients treated with ED. However, none of these reached statistical significance. For hematological toxicities, the risk of all-grade neutropenia (OR = 0.28, 95 % CI: 0.14-0.57), grade ≥ 2 leucopenia (OR = 0.43, 95 % CI: 0.22-0.84), grade ≥ 2 neutropenia (OR = 0.34, 95 % CI: 0.17-0.67), and grade ≥ 3 neutropenia (OR = 0.28, 95 % CI: 0.12-0.63) was significantly decreased. There is no firm evidence confirming the preventive effect of an ED against OM or diarrhea. However, an ED may potentially be helpful in preventing neutropenia and leucopenia.

An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial).

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to have comparable effectiveness or better to ATRA and chemotherapy (CHT) in non-high-risk acute promyelocytic leukemia (APL). However, the efficacy of ATRA-ATO compared to ATRA-ATO plus CHT in high-risk APL remains unknown. Here we performed a randomized multi-center non-inferiority phase III study to compare the efficacy of ATRA-ATO and ATRA-ATO plus CHT in newly diagnosed all-risk APL to address this question. Patients were assigned to receive ATRA-ATO for induction, consolidation, and maintenance or ATRA-ATO plus CHT for induction followed by three cycles of consolidation therapy, and maintenance therapy with ATRA-ATO. In the non-CHT group, hydroxyurea was used to control leukocytosis. A total of 128 patients were treated. The complete remission rate was 97% in both groups. The 2-year disease-free, event-free survival rates in the non-CHT group and CHT group in all-risk patients were 98% vs 97%, and 95% vs 92%, respectively (P = 0.62 and P = 0.39, respectively). And they were 94% vs 87%, and 85% vs 78% in the high-risk patients (P = 0.52 and P = 0.44, respectively). This study demonstrated that ATRA-ATO had the same efficacy as the ATRA-ATO plus CHT in the treatment of patients with all-risk APL.

Anti-inflammatory effects of Morchella esculenta polysaccharide and its derivatives in fine particulate matter-treated NR8383 cells.

Fine particulate matter (PM2.5) exposure could cause many acute and chronic respiratory diseases. In this study the protective effects of polysaccharide from Morchella esculenta (FMP-1) and its derivatives against PM2.5-induced inflammation were evaluated. By flow cytometry and ELISA analysis, sulfated polysaccharide SFMP-1 showed the best protective effect in reducing PM2.5-induced cell death, cell apoptosis and production of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), which was accompanied by a diminished level in reactive oxygen species (ROS) formation caused by PM2.5 in rat alveolar macrophage NR8383 cells. Furthermore, the mechanism was studied by immunofluorescence, qRT-PCR and western blotting. SFMP-1 could down-regulate the expression of inducible NO synthesis (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels in PM2.5-treated cells. The PM2.5-induced phosphorylation of nuclear factor-kappa B (NF-κB) was also reduced through suppressing nuclear translation of the NF-κB and inhibiting the degradation and phosphorylation of IκBα. These results indicated that SFMP-1 could protect NR8383 cells from PM2.5-induced inflammation by inhibiting NF-κB activation.

Glutathione-sensitive PEGylated curcumin prodrug nanomicelles: Preparation, characterization, cellular uptake and bioavailability evaluation.

The anti-tumor efficacy of curcumin can be markedly improved by nano-drug self-delivery systems with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, a type of novel, glutathione (GSH)-responsive, PEGylated prodrug nano-micelles (PPNMs) was prepared by self-assembly of curcumin-s-s-vitamin E/mPEG2k-DSPE mixture. The PPNMs (entrapment efficiency: 96.7%) was acceptably stable in water with a mean particle size of 29.84 nm. Compared with curcumin-loaded mPEG2k-DSPE nano-micelles (CUR-NMs), PPNMs showed a higher drug loading (1.68% vs 27.3%) and remarkably improved the chemical stability of curcumin in phosphate buffer saline (PBS) (pH = 7.4), 10% FBS culture medium, and rat plasma. In vitro release study showed that PPNMs could redox responsively control the release of curcumin from the prodrug. Moreover, PPNMs showed a cytotoxicity in HepG2 cells similar to that of the free curcumin; however, when the HepG2 cells were pretreated with 1 mM GSH, PPNMs displayed a markedly enhanced cytotoxicity and cellular uptake than the free curcumin. After intravenous injection, PPNMs showed an increased half-life in blood circulation (10.6-fold) and bioavailability (107-fold) compared with the free curcumin injection. Altogether, the prodrug nano-micelles represent a promising preparation for sustained and controlled delivery of curcumin with enhanced antitumor activity.

[Relationship between the Therapeutic Dose of Arsenic Trioxide and Relapse in Acute Promyelocytic Leukemia].

OBJECTIVE: To analyze the correlation of ATO therapeutic dose with the relapse of patients with acute promyelocytic leukemia (APL) and to investigate the optimal dose and courses of ATO. METHODS: The clinical data of 102 patients with APL from January 2008 to June 2015 were analyzed retrospectively. The clinical characteristics of APL patients in relapsed group and maintained remission group were compared. According to ATO dose in 2 years recommended in chinese guideline as criteria of grouping, the patients were divided into ATO high and low dose groups, then the relapse rate in groups was compared. The cut-off value of ATO dose was analyzed by ROC curve. RESULTS: Univariate analysis showed that the relapse rate in high ATO and low ATO groups on 2 year treatment was 2.5% and 17.7% respectively (P<0.05); multiple variate analysis demonstrated that the ATO dose>22.4 mg/kg on 2 year treatment was independent preventive factor for the relapse of APL (OR=0.119, P<0.05). The ROC curve showed that the cut-off value of ATO dose on 2 year treatment was 8.765 mg/kg. The relapse rate of APL in group of ATO dose >8.765 mg/kg group was significantly lower than that in group of ATO dose <8.765 mg/kg. CONCLUSION: The relapse of APL relates with used ATO dose, sufficient use of ATO dose can decrease the relapse rate of APL.

[Relationship between Peripheral Blood White Blood Cell Count and Early Death Rate in Patients with Acute Promyelocytic Leukemia].

OBJECTIVE: To investigate the relationship between peripheral white blood cell count and early death rate of the patients with acute promyelocytic leukemia (APL). METHODS: Through retrospective study, the relationship of early death rate in 116 cases newly diagnosed APL patients with maximum of peripheral blood white blood cell count should be analyzed before and after induction therapy as well as in the whole course of disease during the past 8 years. RESULTS: There was a close relationship between the peripheral white blood cell count and the early death rate in APL patients. Peripheral blood white blood cell count in the early died patients was significantly higher than that of the survival patients (P<0.05). ROC analysis showed that the highest risk threshold of peripheral white cell count was 70×109/L (P<0.05) before treatment, while the highest risk threshold after treatment and in the whole course of disease were 96.4×109/L(P<0.05) and 91.5×109/L(P<0.01) respectively. The dealth rate of patients with highest risk threshold was significantly increased (P<0.05). CONCLUSION: The highest peripheral blood white blood cell count closely relates with the early death rate of patients at different time points in the whole course of disease. Control of peripheral white blood cell count may effectively reduce the early death rate of APL patients.

Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation.

Cardiac glycosides could increase intracellular Ca2+ ion by inhibiting the Na+/K+ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety profile and tumor targetablility of cardiac glycosides, we designed octreotide conjugated periplocymarin, a cardiac glycoside isolated from Cortex periplocae. The conjugate showed higher cytotoxicity on MCF-7 cells and HepG2 tumor cells (SSTRs overexpression) but much less toxicity in L-02 normal cells. Tissue distribution studies of the conjugate using H22 tumor model in mice showed higher accumulation in tumor and lower distribution in heart and liver than periplocymarin. Furthermore, in vivo anticancer effects of the conjugate on mice bearing H22 cancer xenografts confirmed enhanced anti-tumor efficacy and decreased systemic toxicity. Altogether, octreotide-conjugated periplocymarin demonstrated tumor selectivity and may be useful as a targeting agent to improve the safety profile of cardiac glycosides for cancer therapy.

Ergosterol-loaded poly(lactide-co-glycolide) nanoparticles with enhanced in vitro antitumor activity and oral bioavailability.

AIM: Ergosterol is a plant sterol with anti-tumor and anti-angiogenic activities, but is poorly soluble. In this study, we attempted to enhance its anti-tumor action and oral bioavailability via poly(lactide-co-glycolide) (PLGA) nanoparticle encapsulation. METHODS: Ergosterol-loaded PLGA nanoparticles (NPs/Erg) were prepared using the emulsion/solvent evaporation technique. Their physicochemical properties were characterized, and their cytotoxicity against human cancer cell lines was evaluated with MTT assay. The pharmacokinetics and tissue distribution of NPs/Erg were investigated in rats and mice, respectively. RESULTS: NPs/Erg were spherical in shape with a particle size of 156.9±4.8 nm and a Zeta potential of -19.27±1.13 mV, and had acceptable encapsulation efficiency and loading capacity. NPs/Erg exerted much stronger cytotoxicity against human cancer cells than the free ergosterol, and showed significantly reduced IC50 values (14.69±0.48 µg/mL in glioma U251 cells; 9.43±0.52 µg/mL in breast cancer MCF-7 cells; 4.70±0.41 µg/mL in hepatoma HepG2 cells). After oral administration of a single dose in rats, NPs/Erg displayed a prolonged plasma circulation with a 4.9-fold increase of oral bioavailability compared with the free ergosterol. After mice received NPs/Erg, the ergosterol in NPs/Erg was rapidly distributed in stomach, kidneys, liver, brain, spleen, and virtually non-existent in heart and lungs. The presence of NPs/Erg in brain was particularly improved compared with the free ergosterol. CONCLUSION: The PLGA nanoparticles serve as a promising carrier for the poorly soluble ergosterol and significantly improve its bioavailability, biodistribution and in vitro anti-tumor activities.

Segetoside I, a plant-derived bisdesmosidic saponin, induces apoptosis in human hepatoma cells in vitro and inhibits tumor growth in vivo.

Segetoside I is a plant-derived bisdesmosidic saponin from Vaccaria segetalis (Neck) with reported anticancer activities. This development has raised an interest in the therapeutic potential of segetoside I. Here, we report the in vitro and in vivo antitumor activities of segetoside I against some selected cancer cell lines (HepG2, human hepatoma; H22, mouse hepatoma; MCF-7, breast cancer; U251, gliocoma; BGC, HGC & SGC, gastric cancinoma; Lovo-1,colon cancer). MTT bioassay analysis showed that HepG2 cells were the most sensitive to segetoside I compared with other cancer cell lines, with lower toxicity in healthy mouse embryonic fibroblast cells. Segetoside I pretreatment of HepG2 resulted in apoptotic induction, dose-dependent DNA fragmentation, inhibition of cell migration, up-regulation of Bax and down-regulation of Bcl-2, which indicated that an apoptotic signaling event could have been initiated. The segetoside I also suppressed hepato-tumour growth in mice with virtually no cytotoxicity and prolonged animal survival, making it a strong oncology drug agent. These findings showed that segetoside I exhibited its antitumor activity via apoptotic induction and significantly support the possible application of the antitumor agent as a potential chemotherapeutic candidate worthy of further investigations.

Tumor targeted delivery of octreotide-periplogenin conjugate: Synthesis, in vitro and in vivo evaluation.

Periplogenin (PPG), a cardiac glycoside prepared from Cortex periplocae, with similar structure to bufalin, has been found to induce apoptosis in many tumor cells. However, lots of cardiac glycosides possessing strong antitumor activity in vitro have still not passed phase I clinical trials, mostly due to poor tumor selectivity and systemic toxicity. To overcome this drawback, we designed octreotide-periplogenin (OCT-PPG) conjugate by coupling PPG-succinate to the amino-terminal end of octreotide. In comparison with free PPG, the conjugate exhibited significantly stronger cytotoxicity on HepG2 cells (SSTRs overexpression) but much less toxicity in L-02 cells. After intravenous injection of OCT-PPG conjugate into H22 tumor-bearing mice, its total accumulation in tumor was 2.3 fold higher than that of free PPG, but was 0.71- and 0.84-fold lower in heart and liver, respectively, suggesting somatostatin-mediated target delivery of PPG into the tumor tissue and reduced distribution in heart and liver. In vivo studies using H22 tumor model in mice confirmed the remarkable therapeutic effect of this conjugate. These results suggested that OCT-PPG conjugate could provide a new approach for clinical application of cardiac glycosides and as a targeting agent for cancer therapy.

The correlation between neurosteroids and neurotransmitters with liver yang rising and liver qi stagnation types of premenstrual syndrome.

BACKGROUND: To investigate neural-reproductive hormonal basis of liver yang rising (LYR), liver qi stagnation (LQS) premenstrual syndrome (PMS), and to develop standardized diagnostic criteria for PMS. METHODS: HPLC, HPLC-MC, ELISA and radioimmunoassay were used to compare levels of serum hormones, plasma neurotransmitters and neurosteroids between LYR PMS patients, LQS PMS patients and healthy controls (30 subjects in each group). RESULTS: Of the measures, all three groups exhibited no significant differences during the follicular phase. In contrast, during the luteal phase, LYR PMS testosterone levels tended to be higher than controls, while dopamine and 5-HT of the LYR PMS group were significantly higher. Conversely, γ-aminobutyric acid in the LYR PMS group was significantly lower than controls (p < 0.05). On the other hand, epinephrine and norepinephrine levels in both PMS groups were significantly higher than controls (p < 0.05), while pregnenolone and allopregnanolone of LYR and LQS groups were significantly lower than controls, with dehydroepiandrosterone (DHEA) being significantly higher than controls (p < 0.05). The ratios of DHEA/allopregnanolone and DHEA/pregnenolone of both PMS groups were significantly higher than the control group, with the LYR PMS group ratios being significantly higher than in the LQS PMS group (p < 0.05). CONCLUSION: The decrease in pregnenolone and allopregnenolone, increase in DHEA, DHEA/allopregnanolone and DHEA/pregnenolone during the luteal phase may be one of the biological bases for anger in LYR PMS patients and depression in LQS PMS patients.

[Signal transduction pathway for TNF-induced IL-6 release from mast cells].

AIM: To investigate the effect of TNF on release of IL-6, IL-10 and histamine from mast cells and to explore its potential signal transduction pathway. METHODS: After stimulation of various concentrations of TNF, the P815 cells were analyzed by cellular activation of signal ELISA(CASE) to detect phosphorylation of ERK, p38 and STAT3, and the supernatants were collected and analyzed by ELISA to quantify release of IL-6, IL-10 and histamine from the cells. RESULTS: Compared with the untreated control, increased IL-6 release was detected in TNF-stimulated P815 cells (P<0.05). Pretreatment of PD98059 or U0126 inhibited TNF-induced IL-6 release and ERK phosphorylation in P815 cells (P<0.05), whereas pretreatment of SB203580 or AG490 hardly affect IL-6 release, with little effect on phosphorylation of p38 and STAT3 respectively. CONCLUSION: TNF induced IL-6 release from P815 cells may involve activation of ERK signalling pathway.

Ferulic acid-induced anti-depression and prokinetics similar to Chaihu-Shugan-San via polypharmacology.

Selective serotonin reuptake inhibitors (SSRIs), one of popular antidepressants as "one-compound-one-target" paradigm, cannot but discontinue because of inhibiting gut movement. Traditional Chinese medicine (TCM) Chaihu-Sugan-San (CSS) can simultaneously exert anti-depression and prokinetics. From this thread, we aimed to find a new antidepressant with polypharmacological mechanisms. In vivo antidepressive and prokinetic comparisons between CSS and its absorbed compound ferulic acid (FA) were made. And FA's action mechanisms involved in monoaminergic systems, HPA axis and gastrointestinal peptide ghrelin was then studied in forced swimming test (FST) of rat. Lastly, the jejunal contraction activity evoked by FA was measured in vitro. Compared with vehicle, FA reduced immobility time, increased locomotor activity, accelerated gastric emptying and intestinal transit similar to CSS whose absorbable component FA was identified in hippocampus and jejunum. FA's prokinetics in vivo was further supported by its jejunal contraction in vitro. FA-induced anti-immobility was prevented by pretreated with PCPA, WAY-100635, ketanserin, sulpiride, SCH233390, haloperidol and yohimbine, respectively. CRH, ACTH and 5-HT were significantly decreased, but ghrelin was apparently increased compared with vehicle. In summary, FA induced anti-depression and prokinetics similar to CSS via inhibiting serotonin, norepinephrine and dopamine reuptakes, regulating HPA axis, increasing ghrelin and stimulating jejunal contraction simultaneously.

[Studies on the anti-inflammation effect of the TCM prescription of a combination of monkshood root with peony root].

OBJECTIVE: To make a comparison between the single and combined use of Monkshood Root and Peony Root to observe the anti-inflammation effect in the experimental animals. METHOD: The experimental inflammatory models were adopted, i.e. adjuvant-induced polyarthritis carrageenan-induced or formaldehyde-induced rat paw edema, and cotton pellet-induced granuloma formation in rats xylene-induced mouse ear edema, exudation of abdominal blood capillaries of mice, etc. RESULT: The anti-inflammafion effect of Monkshood Root was weaker than that of Peony Root or Peony Root combined with Monkshood Root. It was found that anti-inflammation effect with the drug-cooperation was enhanced more significantly in the formaldehyde-induced or adjuvant-induceed arthritis models than in the carrageenan-induced rat paw edema and other inflammatory models either in the large dosage of 1:1 proportion or in the small dosage of 1:2 proportion. CONCLUSION: The drug-cooperation has a good selective and synergic effect on anti-inflammation.