Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

Self-assembled Gallic acid loaded lecithin-chitosan hybrid nanostructured gel as a potential tool against imiquimod-induced psoriasis.

Increased thickness of the skin and hyperproliferation of keratinocyte cell is the main obstacle in the treatment of psoriasis. Gallic Acid (GA) has shown efficacious results against the hyperproliferation of keratinocytes while lipid-polymer loaded hybrid nanoparticles (LPHNs) have an edge over lipidic and polymeric nanoparticles considering drug loading, controlled release, stability, and retention. The LPHNs were optimized using Box-Behnken method and was further characterized by FTIR, DSC and Zetasizer. The optimized preparation demonstrated a size of 170.5 ± 0.087 nm and a PDI of 0.19 ± 0.0015, respectively. The confocal study has suggested that the hybrid nanosystem enhanced the drug penetration into the deeper layer with a higher drug release of 79 ± 0.001% as compared to the gallic acid-loaded gel. In addition, the formulation significantly reduced PASI score and splenomegaly without causing any serious irritation. The morphological study of the spleen suggested that the prepared formulation has well controlled the disease compared to the marketed formulation while maintaining a normal level of immune cells after treatment. Hence GALPHN could be accepted as one of the excellent vehicles for the topical conveyance of GA (gallic acid) due to enhanced penetration, and good retention, along with fewer side effects and higher efficacy of the GALPHN gel against imiquimod (IMQ) induced psoriasis.

Amelioration effects of the soybean lecithin-gallic acid complex on iron-overload-induced oxidative stress and liver damage in C57BL/6J mice.

CONTEXT: Gallic acid (GA) and lecithin showed important roles in antioxidant and drug delivery, respectively. A complex synthesized from GA and soybean lecithin (SL-GAC), significantly improved bioavailability of GA and pharmacological activities. However, the antioxidant activity of SL-GAC and its effect on iron-overload-induced liver injury remains unexplored. OBJECTIVE: This study investigates the antioxidant properties of SL-GAC in vitro and in mice, and its remediating effects against liver injury by iron-overloaded. MATERIALS AND METHODS: In vitro, free radical scavenging activity, lipid peroxidation inhibition, and ferric reducing power of SL-GAC were measured by absorbance photometry. In vivo, C57BL/6J mice were randomized into 4 groups: control, iron-overloaded, iron-overloaded + deferoxamine, and iron-overloaded + SL-GAC. Treatments with deferoxamine (150 mg/kg/intraperitioneally) and SL-GAC (200 mg/kg/orally) were given to the desired groups for 12 weeks, daily. Iron levels, oxidative stress, and biochemical parameters were determined by histopathological examination and molecular biological techniques. RESULTS: In vitro, SL-GAC showed DPPH and ABTS free radicals scavenging activity with IC50 values equal to 24.92 and 128.36 µg/mL, respectively. In C57BL/6J mice, SL-GAC significantly reduced the levels of serum iron (22.82%), liver iron (50.29%), aspartate transaminase (25.97%), alanine transaminase (38.07%), gamma glutamyl transferase (42.11%), malondialdehyde (19.82%), total cholesterol (45.96%), triglyceride (34.90%), ferritin light chain (18.51%) and transferrin receptor (27.39%), while up-regulated the levels of superoxide dismutase (24.69%), and glutathione (11.91%). CONCLUSIONS: These findings encourage the use of SL-GAC to treat liver injury induced by iron-overloaded. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

Efficacy and safety of iodized lecithin tablets versus spironolactone in alleviating central serous retinopathy among Chinese patients with uncontrolled diabetes.

To compare the effectiveness and safety of spironolactone versus lecithin-bound iodine in patients with central serous retinopathy (CSR). Chinese diabetes patients aged>18 years with CSR with persistent increased level of subretinal fluid (SRF) were enrolled. Subjects were randomized to receive either oral lecithin-bound iodine (390µg/kg/day) or oral spironolactone (50mg/day) for 6 months. A total of 200 patients were randomized and completed the study. Compared to spironolactone group, patients treated with lecithin-bound iodine had greater proportion of eye with complete resolution (87% vs 81%, p>0.005). Higher improvement in height of SRF was observed in lecithin-bound iodine-treated patients as compared with Spironolactone-treated patients (91.2[87.5] vs 142.5 [121.1]; p>0.005). However, no statistically significant difference was observed on none of comparisons. Compared to Spironolactone, the patients treated with lecithin-bound iodine had greater improvement in lesion size, central macular thickness and best-corrected visual acuity. However, no statistically significant difference was observed in any of parameter assessed. (p>0.005). The results of the present study suggested that the lecithin-bound iodine was found more effective (nnumerically) than spironolactone in Chinese diabetes patients with CSR.

Delayed-Release Phosphatidylcholine Is Effective for Treatment of Ulcerative Colitis: A Meta-Analysis.

BACKGROUND: Phosphatidylcholine (PC) is intrinsically missing in intestinal mucus of patients with ulcerative colitis. Topical supplementation with delayed intestinal release PC formulations is assumed to compensate this lack. Three monocenter randomized controlled trials (RCTs) with a 30% PC-containing lecithin were successful, whereas 1 trial with >94% PC-containing lecithin failed. OBJECTIVES: Evaluation of 30% PC-containing lecithin provided in a delayed intestinal release formulation for treatment efficacy of ulcerative colitis was evaluated by meta-analysis of 3 RCTs. METHODS: Meta-analysis of 3 studies was performed using RevMan 5.3 software. Odds ratio (OR) and 95% Cl were calculated for remission, clinical and endoscopic improvement, histology, and life quality. p values <0.05 were accepted as significant. RESULTS: The meta-analysis of 3 RTCs with 160 included patients with ulcerative colitis verified that PC improved the rate of remission (OR = 9.68), as well as clinical (OR = 30.58) and endoscopic outcomes (OR = 36.73). Within the available patient population, also histology and quality of life became better. All effects were significant over placebo. Achieved remission was maintained in a higher percentage of patients under intestinal-release PC formulation than placebo. The profile of adverse events was identical to the placebo population. CONCLUSIONS: A 30% PC-containing lecithin in delayed intestinal release formulation improves clinical and endoscopic outcomes, histologic activity, and quality of life in patients with ulcerative colitis. For the patients, lack of adverse events is an important consideration.

Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells.

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 µg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg-1·d-1, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

Effect of soy lecithin on fatigue and menopausal symptoms in middle-aged women: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Lecithin is a complex mixture of phospholipids which compose lipid bilayer cell membranes. Lipid replacement therapy, or administration of phospholipids for the purpose of repairing the dmaged cell membranes, had been shown to alleviate fatigue. The present study aimed to investigate the effect of soy lecithin on fatigue in middle-aged women, as well as other menopausal symptoms and various health parameters. METHODS: This randomized, double-blind, placebo-controlled study included 96 women aged 40 to 60 years who complained of fatigue. The participants were randomized to receive active tablets containing high-dose (1200 mg/day; n = 32) or low-dose (600 mg/day; n = 32) soy lecithin, or placebo (n = 32), for 8 weeks. The following parameters were evaluated: age, menopausal status, lifestyle factors, physical and psychological symptoms of menopause, subjective symptoms of insomnia and fatigue, body composition, cardiovascular parameters, and physical activities and objective sleep states obtained from actigraphy before and 4 and 8 weeks after treatment. Fatigue was evaluated using the Profile of Mood States (POMS)-brief, Menopausal Health-Related Quality of Life questionnaire, Chalder Fatigue Scale, and Brief Fatigue Inventory. RESULTS: Eighty-nine women completed the study. There were no significant differences in the changes in Chalder Fatigue Scale score (placebo vs low-dose vs high-dose groups: -2.9 ± 1.1, -3.2 ± 1.1, and -3.5 ± 1.0; P = 0.79). On the other hand, the improvements were greater in the high-dose group compared with the placebo group concerning vigor scores in the POMS-brief (1.9 ± 0.7 vs 0.2 ± 0.6; P = 0.02), diastolic blood pressure (-4.1 ± 1.8 vs 1.2 ± 1.9; P = 0.05), and cardio-ankle vascular index (-0.4 ± 0.2 vs 0.07 ± 0.1; P = 0.03) after 8 weeks of treatment. CONCLUSIONS: High-dose (1200 mg/day) soy lecithin not only increases vigor, but also lowers the diastolic blood pressure and cardio-ankle vascular index in middle-aged women who present with fatigue. TRIAL REGISTRATION: UMIN-CTR UMIN000017127 .

Trichuris suis ova, lecithin and other fancy molecules.

During the last 20 years, treatment paradigms as well as drugs used for IBD have changed significantly. However, there are still many unmet needs and a significant number of patients needing better therapy. It is obvious from this situation that many attempts have been made to implement new drugs and treatment algorithms including biologicals, new formulations of old drugs and 'fancy molecules or approaches'. For about 10 years, the application of Trichuris suis ova has been promoted and used in quite a number of patients. Two early studies suggested positive effects in ulcerative colitis as well as in Crohn's disease. These studies were based on experimental data in animal models as well as in vitro experiments. However, two large randomized controlled trials were not able to provide significant clinical effects in active Crohn's disease as compared to placebo, although a biological reaction (eosinophilia) was found. Another approach is the use of locally released phosphatidylcholine in ulcerative colitis. This approach is based on decreased phosphatidylcholine concentrations in the colonic mucus in patients, and showed positive effects in a number of monocentric trials in steroid-refractory and chronic active ulcerative colitis. A dose-finding study gave a positive signal in the highest-dose group and this approach is being tested further in controlled trials. Many other 'fancy molecules' including cannabis, vitamin D, thalidomide, hyaluronic acid, lidocaine, clonidine, chondroitin sulfate, naltrexone and melatonin have been tested in patients with claims of success. For most of those, however, controlled data in appropriate studies are lacking. Many more substances have been used in animal models and are probably applied in individual patients. Results of preliminary studies on some of the molecules mentioned are presented.

Effect of pectin, lecithin, and antacid feed supplements (Egusin®) on gastric ulcer scores, gastric fluid pH and blood gas values in horses.

BACKGROUND: The objectives of this study were to evaluate the effects of two commercial feed supplements, Egusin 250® [E-250] and Egusin SLH® [E-SLH], on gastric ulcer scores, gastric fluid pH, and blood gas values in stall-confined horses undergoing feed-deprivation. METHODS: Nine Thoroughbred horses were used in a three-period crossover study. For the three treatment groups, sweet feed was mixed with E-250, E-SLH, or nothing (control group) and fed twice daily. Horses were treated for 21 days, then an additional 7 days while on an alternating feed-deprivation model to induce or worsen ulcers (period one). In periods two and three, horses (n=6) were treated for an additional 7 days after feed-deprivation. Gastroscopies were performed on day -1 (n=9), day 21 (n=9), day 28 (n=9) and day 35 (n=6). Gastric juice pH was measured and gastric ulcer scores were assigned. Venous blood gas values were also measured. RESULTS: Gastric ulcers in control horses significantly decreased after 21 days, but there was no difference in ulcer scores when compared to the Egusin® treated horses. NG gastric ulcer scores significantly increased in E-250 and control horses on day 28 compared to day 21 as a result of intermittent feed-deprivation, but no treatment effect was observed. NG ulcer scores remained high in the control group but significantly decreased in the E-SLH- and E-250-treated horses by day 35. Gastric juice pH values were low and variable and no treatment effect was observed. Mean blood pCO2 values were significantly increased two hours after feeding in treated horses compared to controls, whereas mean blood TCO2 values increased in the 24 hour sample, but did not exceed 38 mmol/l. CONCLUSIONS: The feed-deprivation model increased NG gastric ulcer severity in the horses. However, by day 35, Egusin® treated horses had less severe NG gastric ulcers compared to untreated control horses. After 35 days, Egusin® products tested here ameliorate the severity of gastric ulcers in stall-confined horses after feed stress.

The Antioxidant and anti-inflammatory Activity of Selenium and Lecithin Combination Against ethanol-induced Gastric Ulcer in mice via Modulating IGF-1/PTEN/Akt/FoxO3a Signaling.

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1ß levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling.

Lecithin as a therapeutic agent in ulcerative colitis.

Lecithin [phosphatidylcholine (PC)] was shown to account for more than 70% of total phospholipids within the intestinal mucus layer. It is arranged in lamellar membranes (surfactant-like particles) and establishes a hydrophobic barrier preventing invasion of the colonic commensal microbiota. In ulcerative colitis (UC), the mucus PC content was demonstrated to be reduced by about 70%, irrespective of the presence of inflammation. This may be of primary pathogenetic significance allowing bacteria to enter the mucus and induce mucosal inflammation. Therefore, a new therapeutic strategy is being developed to substitute the missing mucus PC content in UC. Indeed, a delayed-release PC formulation was able to compensate the lack of PC and improve the inflammatory activity. In randomized controlled studies, delayed-release PC was proven to be clinically and endoscopically effective, which now awaits a phase III authority approval trial.

[Using hepatomaks forte in the treatment of chronic alcoholic hepatitis].

Installed significantly more pronounced positive effect on clinical manifestations and laboratory indicators of liver in patients with chronic alcoholic hepatitis who received within 4 weeks of basal therapy in conjunction with Gepatomax Forte in comparison with a group of patients with chronic alcoholic hepatitis who received during the same time only basic therapy. Side adverse effects in the group of patients receiving Gepatomax Forte were not registered.

An alkalinizing oral rehydration solution containing lecithin-coated citrus fiber is superior to a nonalkalinizing solution in treating 360 calves with naturally acquired diarrhea.

The aim of this field study was to compare the efficacy and cost of 2 commercially available oral rehydration therapy (ORT) solutions in treating dairy calves with naturally acquired diarrhea. A total of 1,349 newborn Holstein-Friesian calves were prospectively enrolled in the study. Calves were housed in individual hutches and fed a mixture of pasteurized hospital milk and an all-milk protein milk replacer twice per day. Calves were monitored twice each day from d 2 of life until 30 d of age for the presence or absence of diarrhea, and were assigned a fecal score and a hydration score at each examination. Calves that developed mild to severe diarrhea that did not need intravenous fluids and did not have clinical evidence of concurrent disease (n = 360) were assigned randomly to receive 1 of 2 commercial ORT solutions: a hypertonic alkalinizing ORT containing lecithin-coated citrus fibers (Diaque, group D, n = 180; Boehringer Ingelheim, Ingelheim, Germany), and an isotonic nonalkalinizing ORT (RE-SORB, group R, n = 180; Pfizer Animal Health, New York, NY) for 2 to 8d; the duration of treatment depended on whether diarrhea was still present. No significant differences were observed in mortality rates or treatment failure rates between the 2 treatment groups. Fecal consistency returned to normal more quickly in group D calves than in group R calves; consequently, group D calves were treated for 1d less than were group R calves. The increase in body weight after 4d of treatment was larger in group D than in group R. The average daily gain from birth to weaning in calves that did not develop concurrent disease (such as pneumonia) during the study period tended to be higher in group D calves (0.53±0.11 kg/d) than in group R calves (0.51±0.09 kg/d). The smaller number of treatments at a lower cost per treatment produced a cost advantage of $4.82 per treated calf in group D calves compared with group R calves. Our findings support the concept that milk should continue to be fed to diarrheic calves that are being administered an ORT solution in order to maintain growth.

[Efficacy of enteric lecithin (phosphatidylcholine) in the treatment of ulcerative colitis: a meta-analysis]. / Wirksamkeit von darmlöslichem Lecithin (Phosphatidylcholin) zur Behandlung der Colitis ulcerosa : Eine Metaanalyse.

BACKGROUND: Phosphatidylcholine is an essential component of the intestinal mucus and serves as a protective shield against the ingress of bacteria from the stool. In the intestinal mucus of patients with ulcerative colitis, phosphatidylcholine is reduced by 70%, which makes the intestine susceptible to bacterial inflammation. Local application by administering enteric phosphatidylcholine could compensate for this deficiency. METHOD: A summary analysis of three clinical studies published until now with 160 included patients with ulcerative colitis was performed. RESULTS AND CONCLUSION: The meta-analysis showed that lecithin enriched with phosphatidylcholine and microencapsulated with Eudragit S-100 significantly improved the remission rate as well as the clinical and endoscopic picture. There was also an improvement in histology and quality of life. All parameters were significantly superior to placebo. The remission achieved was maintained significantly longer with enteric lecithin than with placebo. The side effect profile was identical to the placebo group, which is particularly important for the patients. In complementary medicine, phosphatidylcholine can be seen as protection for the intestines.

Treatment with phosphatidylcholine of patients with nonalcoholic fatty liver disease: a prospective pilot study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is characterized by a complex clinical picture that includes nonalcoholic steatohepatitis and cirrhosis. In the last decades, several studies have shown that NAFLD increases the risk of cardiovascular diseases. In a prospective pilot study, the benefit of treatment with phosphatidylcholine in NAFLD patients has been assessed. METHODS: Thirty patients with NAFLD were enrolled. All received treatment with phosphatidylcholine (Essentiale® Forte N; Sanofi, Paris, France) 300 mg capsules, administered 2 at time orally, 3 times a day with meals for three months. The clinical and laboratory parameters before and after treatment were compared. RESULTS: After the administration of Essentiale® Forte N (Sanofi) the level of alanine aminotransferase (ALT) decreased by 59.6% (P<0.05) and that of aspartate transaminase (AST) decreased by 75.4% (P<0.05). Moreover, after treatment, an increase in antioxidant enzymes superoxide dismutase by 48% (P<0.05) and glutathione peroxidase by 48.1% (P<0.05) was observed. CONCLUSIONS: The results of the study indicate that treatment with Essentiale® Forte N (Sanofi) for 3 months was associated with a significant decrease in transaminase levels, in the activity of lipid peroxidation markers and with an increase in the level of antioxidant enzymes.

DT7 peptide-modified lecithin nanoparticles co-loaded with γ-secretase inhibitor and dexamethasone efficiently inhibit T-cell acute lymphoblastic leukemia and reduce gastrointestinal toxicity.

T-cell acute lymphoblastic leukemia (T-ALL) is a serious hematologic malignancy and glucocorticoid resistance is the main recurrent cause for a high relapsed and death rate. Here, we proposed an effective therapeutic regimen of combining gamma-secretase inhibitors (GSIs) with dexamethasone (DEX) to overcome glucocorticoid resistance. Moreover, the bone marrow targeting DT7 peptide-modified lecithin nanoparticles co-loaded with DEX and GSI (TLnp/D&G) were developed to enhance T-ALL cells recognition and endocytosis. In vitro cytotoxicity studies showed that TLnp/D&G significantly inhibited cell survival and promoted apoptosis of T-ALL cells. Mechanically, we found that GSIs promoted DEX-induced cell apoptosis by two main synergetic mechanisms: 1) GSIs significantly upregulated glucocorticoid receptor (GR) expression in T-ALL and restored the glucocorticoid-induced pro-apoptotic response. 2) Both DEX and GSI synergistically inhibited BCL2 and suppressed the survival of T-ALL cells. Furthermore, in vivo studies demonstrated that TLnp/D&G showed high bone marrow accumulation and better antileukemic efficacy both in leukemia bearing models and in systemic Notch1-induced T-ALL models, with excellent biosafety and reduced gastrointestinal toxicity. Overall, our study provides new strategies for the treatment of T-ALL and promising bone marrow targeting systems with high transformation potential.

Lecithin-based novel cationic nanocarriers (Leciplex) II: improving therapeutic efficacy of quercetin on oral administration.

The objective of the present investigation was to evaluate ability of the novel self-assembled phospholipid- based cationic nanocarriers (LeciPlex) in improving the therapeutic efficacy of a poorly water-soluble natural polyphenolic agent, quercetin (QR), on oral administration. Quercetin loaded LeciPlex (QR-LeciPlex) were successfully fabricated using a biocompatible solvent Transcutol HP. The QR-LeciPlex were characterized for particle size, encapsulation efficiency, zeta potential, and particle morphology by cryo-TEM. UV and fluorescence spectral characterization was carried out to find out the association of QR with LeciPlex. Small angle neutron scattering studies (SANS) were carried out to understand the internal structure of Leciplex and to evaluate the influence of the incorporation of QR in the LeciPlex. Anti-inflammatory and antitumorigenic activity of QR-LeciPlex was determined in comparison to QR suspension to evaluate the potential of LeciPlex in improving oral delivery of QR. QR-LeciPlex exhibited a particle size of ∼400 nm and had excellent colloidal stability. The QR-LeciPlex had a zeta potential greater than +30 mV and exhibited very high encapsulation efficiency of QR (>90%). UV and fluorescence spectral characterization indicated the interaction/association of QR with LeciPlex components. Cryo-TEM studies showed that LeciPlex and QR-LeciPlex have a unilamellar structure. SANS confirmed the unilamellar structure of LeciPlex and indicated that the incorporation of QR does not have any effect on the internal structure of the LeciPlex. QR-LeciPlex exhibited significantly higher anti-inflammatory and antitumorigenic activity (p < 0.01) as compared to that of QR suspension on oral administration.

Nutritional approaches to prevention and treatment of gallstones.

Cholesterol gallstones are among the most common gastrointestinal disorders in Western societies. Individuals with gallstones may experience various gastrointestinal symptoms and are also at risk of developing acute or chronic cholecystitis. Cholecystectomy is the most frequently recommended conventional treatment for symptomatic gallstones. Bile acids (ursodeoxycholic acid or chenodeoxycholic acid) are also used in some cases to dissolve radiolucent stones, but these drugs can cause gastrointestinal side effects and there is a high rate of stone recurrence after treatment is discontinued. Lithotripsy is used in some cases in conjunction with ursodeoxycholic acid for patients who have a single symptomatic non-calcified gallstone. There is evidence that dietary factors influence the risk of developing cholesterol gallstones. Dietary factors that may increase risk include cholesterol, saturated fat, trans fatty acids, refined sugar, and possibly legumes. Obesity is also a risk factor for gallstones. Dietary factors that may prevent the development of gallstones include polyunsaturated fat, monounsaturated fat, fiber, and caffeine. Consuming a vegetarian diet is also associated with decreased risk. In addition, identification and avoidance of allergenic foods frequently relieves symptoms of gallbladder disease, although it does not dissolve gallstones. Nutritional supplements that might help prevent gallstones include vitamin C, soy lecithin, and iron. In addition, a mixture of plant terpenes (Rowachol) has been used with some success to dissolve radiolucent gallstones. The gallbladder flush is a folk remedy said to promote the passage of gallstones. While minimal scientific evidence supports the efficacy of this treatment, anecdotal reports suggest the gallbladder flush may be beneficial for some people.

Effect of liposomes containing antioxidant, phospholipid, and amino acid on skin regeneration after chemical burn.

Liposomes containing natural flavonoid dihydroquercetin, phospholipid lecithin, and zwitterionic amino acid glycine were used for the therapy of glacial acetic acid-induced chemical burn. No inflammatory reaction was observed in the region of wound. The area of postburn injury did not increase in time. Planimetry and histological studies showed that improved skin regeneration was accompanied by repair of hair follicles and sebaceous glands.

Complementary and alternative medicine in the treatment of schizophrenia.

During the past century, many scientific discoveries and industrialization greatly contributed to the progress in medicine and significantly improved a quality of life of psychiatric patients. Schizophrenia is a serious mental disorder. Due to synthesis of numerous high quality antipsychotic medications, a great progress in the treatment of it has been made during the last 50 years. In five thousand years of the recorded history, it is known that in the early times, people used different methods and procedures in the treatment of various psychiatric disorders including schizophrenia. In recent decades after great discoveries, medicine based on facts has also faced a number of disappointments. The medicine gradually begins to understand that some of the alternatives used earlier in centuries are complementary methods that were unnecessarily suppressed and excluded from the treatment. On the other hand, a number of countries where this is legally possible is growing and there is also an increasing number of patients seeking alternative and complementary methods in the treatment of schizophrenia. The aim of this paper is to encourage and reflect upon the meaning of alternative and complementary methods in the treatment of schizophrenia as well as to try and prevent forgetting their meaning whenever it is justified and based on facts.