Statins decrease the risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease:A systematic review and meta-analysis

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma(HCC).Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics.However,it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD.AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD.METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD.The difference in HCC risk between statin users and non-users was calculated among MASLD patients.We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction.RESULTS A total of four studies consisting of 291684 patients were included.MASLD patients on statin therapy had a 60%lower pooled risk of developing HCC compared to the non-statin group[relative risk(RR)=0.40,95%CI:0.31-0.53,I2=16.5%].Patients taking lipophilic statins had a reduced risk of HCC(RR=0.42,95%CI:0.28-0.64),whereas those on hydrophilic statins had not shown the risk reduction(RR=0.57,95%CI:0.27-1.20).The higher(>600)cumulative defined daily doses(cDDD)had a 70%reduced risk of HCC(RR=0.30,95%CI:0.21-0.43).There was a 29%(RR=0.71,95%CI:0.55-0.91)and 43%(RR=0.57,95%CI:0.40-0.82)decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD,respectively.CONCLUSION Statin use lowers the risk of HCC in patients with MASLD.The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.

Milk-derived exosomes as a promising vehicle for oral delivery of hydrophilic biomacromolecule drugs

Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.

Formation of the entorhino-hippocampal pathway: a tracing study in vitro and in vivo

Objective The entorhino-hippocampal pathway is the major excitatory input from neurons of the entorhinal cortex on both ipsilateral and contralateral hippocampus/dentate gyrus. This fiber tract consists of the alvear path, the perforant path and a crossed commissural projection. In this study, the histogenesis and development of the various subsets of the entorhino-hippocampal projection have been investigated. Methods Dil, DiO and fast blue tracing as well as anti-calretinin immunocytochemistry were carried out with prenatal and postnatal rats at different ages. Results The alvear path and the commissural pathway started to develop as early as embryonic day （E） 16, while the first perforant afferents reached the stratum lacunosum-moleculare of the hippocampus at E 17 and the outer molecular layer of dentate gyrus at postnatal day （P） 2, respectively. Retrograde tracing with DiI identified entorhinal neurons in layer II to IV as the origin of entorhino-hippocampal pathway. Furthermore, anti-calretinin immunocytochemistry revealed transitory Cajal- Retzius （CR） cells in the stratum lacunosum-moleculare of the hippocampus from as early as E 16. DiI labeling of entorhinal cortex fibers and combined calretinin-immunocytochemistry showed a close association between CR cells and entorhinal afferents. Conclusion The subsets of entorhino-hippocampal pathway appear in the developmental hippocampus during El6 - P2. The temporal and spatial relationship between CR cell and perforant afferent suggests the role of this cell type as a guiding cue for entorhinal afferents at early cortical development.

Influence of pH Environment on Nasal Absorption of Meptazinol Hydrochloride

Aim To investigate the relationship between pH environment of meptazinolhydrochloride (MEP) and its nasal absorption. Methods In situ nasal peifusion was performed to studythe effect of pH environment on the nasal absorption. Its effect on the transport from nose tobrain was further researched by in vivo experiment. Results In in situ perfusion experiment, thenasal absorption of MEP in basic environment was significantly higher than that in acid condition,but the difference was not observed in in vivo experiment. Conclusion The pH environment ofmeptazinol hydrocloride in formulation cannot be regarded as an important factor influencing nasalabsorption and transport from nose to brain.

复配乳化剂HLB值对壳聚糖精油复合膜物理和结构性能的影响

通过复配吐温和司盘获得不同亲水亲油平衡(hydrophile lipophilic balance,HLB)值的复配乳化剂,探究乳化剂HLB值对壳聚糖精油复合膜的物理和结构性能的影响。结果表明,HLB值在9~15之间,单独乳化剂与精油体积比1∶5和1∶10均可获得较小的精油粒径。乳化剂加入壳聚糖精油复合膜中,随着乳化剂HLB值的升高,膜乳液的粒度逐渐减小。与加入精油的对照膜相比,乳化剂的添加可以提高膜的L*值,降低膜的厚度、膨胀度和水溶性,但乳化剂HLB值对膜的抗拉强度和断裂伸长率影响较小。在乳化剂HLB值11~15之间时,可获得较高的DPPH自由基清除率。从扫描电镜结果来看,乳化剂能显著降低复合膜中精油的粒径。综合来看,HLB值为13时,能获得性能较好的复合膜。

Dinophysis caudata generated lipophilic shellfish toxins in bivalves from the Nanji Islands, East China Sea

A 12-month program of monitoring potentially toxic microalgae(that produce lipophilic shellfi sh toxins; LSTs) and their toxins in bivalves was conducted from April 2006 to March 2007 in the Nanji Islands, East China Sea. Two Dinophysis species, D. caudata and D. acuminata, were identifi ed, and D. caudat a was found to be the dominant species. D. caudata was detected in water samples between April and June 2006, and between February and March 2007. It reached its highest abundances in May, with a mean abundance of 1.38×10 2 cells/L in surface water and 1.25×10 2 cells/L in bottom water(<10 m deep). The temporal distribution of D. caudata was associated with the occurrence of LSTs in bivalve samples, which mostly occurred at the same time as D. caudata blooms, between April and July 2006. All of the cultured bivalves sampled between April and June were contaminated with LSTs, with an average toxicity of 85 μg okadaic acid(OA) eq./100 g meat, which was four times higher than the Chinese regulatory limit(20 μg OA eq./100 g meat). Ten out of fi fteen wild samples(66.7%) collected during the same period were positive for LSTs, and contained an average LST toxicity of 45 μg OA eq./100 g meat(more than twice the regulatory value). Cultured Patinopecten yessoensis collected on 15 May 2006 had the highest toxicity, 320 μg OA eq./100 g meat, and relatively high toxicities(80 to 160 μg OA eq./100 g meat) were found in bivalves until the end of July.

Theoretical and experimental study on lipophilicity and wound healing activity of ginger compounds

Objective:To correlate the chromatographic and computational method to calculate lipophilicity of selected ginger compounds and to observe the effects of log P on wound healing.Methods:Mixtures of acetonitrile and water with acetonitrile content between 95%and 50%v/v in 5%increments were kept separately in 10 different chromatographic chambers,saturated with solvent for 2 h.Spots were observed under UV light atλ=254 nm p-anisaldehyde used as a spraying reagent Theoretical calculation was done using the Alogps 2.1 online program at www.vcclab.org/lab/alogps.For percentage wound contraction,five groups of animal(mice)(25-30 g)of either sex were selected.Wound were created on dorsal surface of animals using toothed forceps,scalpel and pointed scissors.The wound areas were calculated using vernier caliper.After making wound mice were orally administered 35 mg/kg 6-shogoal,6-gingerol,8-gingerol and 10-gingerol respectively.Croup E as the control group received tap water.Results:The Iipophilicity values determined in thin layer chromatography were correlated with the theoretically calculated various log P by linear regression analysis.Significant correlations were found between log P values calculated by software program and the experimental reversedphase thin-layer chromatography data.Order of wound healing property of ginger compounds is directly dependent on lipophilieity i.e.more lipophilic compound has highest activity.Conclusions:Experimentally determined lipophilieity(R_(MO))values were correlated with log P determined by software's and found satisfactory.Lipophilieity(R_(MO)is a useful parameter for the determination and prediction of biological activity of ginger compounds.

Lipophilic extractives of the inner and outer barks from six different Pinus species grown in Indonesia

The chemical compositions of the dichloromethane extracts of inner and outer barks from six Pinus species（P.elliotii,P.oocarpa,P.caribeae,P.merkusii,P.montezumae,and P.insularis） grown in Indonesia were investigated by GC and GC–MS.Generally,the amounts of extractive contents were higher in the inner bark than in the outer bark except for P.merksuii.Fatty acids,monoterpenes,sesquiterpenes,resin acids,triterpenoids,and steroids were detected and quantified.Inner and outer barks differed not only in content of these compounds but also in their composition.Fatty acids and alcohols were the major classes of lipophilic compounds in the outer bark of P.caribeae, P.insularis,and P.montezumae.Steroids and triterpenoids were the dominant compounds identified in the inner bark of P.elliotii,P.insularis,and P.merkusii.Resin acids were the most abundant group in the inner bark of P.oocarpa whereas monoterpenes and sesquiterpenes were recorded in minor quantities in both bark layers of all species.

A novel long-chain acyl-derivative of epigallocatechin-3-O-gallate prepared and purified from green tea polyphenols

Lipophilic tea polyphenols (LTP) were prepared by catalytic esterification of green tea polyphenols (GTP) with hexadecanoyl chloride. A novel long chain acyl derivative of epigallocatechin 3 o gallate (EGCG) was first isolated from purification of LTP by high speed countercurrent chromatography (HSCCC) using a solvent system composed of n hexane ethyl acetate methanol water (1:1:1:1, v/v). The molecular structure of the acyl derivative, Epigallocatechin 3 O gallate 4′ O hexadecanate , was elucidated by means of elemental analysis, IR, 1H NMR and MS spectra.

Influence of different layers of skin on the percutaneous absorption of drugs with different lipophilicity

Objectives: To evaluate the barrier function of different skin layers in the process of percutaneous drug absorption. Methods: In vitro permeability via intact or stripped skin of 6 drugs (5-fluorouracil, theo-phylline, hydroquinone, barbital, isosorbide dinitrate and ketoprofen) with a wide span of lipophilicity were investigated in the patch dosage forms. Results: Characteristic parabolic relations was observed between the permeability (Kp, cm/h) of the drugs with different lipophilicity and their LogPc via either intact or stripped skin. However, due to the absence of the stratum corneum, increased Kp ratio for the tested drugs was proportional to their solubility in water other than their LogKp. When isopropyl myristate was used as absorption promoter of the drugs, the parabolic relationship no longer existed. For the intact skin, increase of Kp ratio of the drugs was enhanced resulting from IPM as drug's LogPc decreased. On the other hand, in the case of stripped skin, this enhancement was positively related to the solubility of the drugs in IPM. Conclusion : These data and methods present a novel approach to describe percutaneous drug absorption via damaged or diseased skin.

Ocular prodrugs: Attributes and challenges

Ocular drug delivery is one of the most attention-grabbing and challenging endeavors among the numerous existing drug delivery systems.From a drug delivery point of view,eye is an intricate organ to investigate and explore.In spite of many limitations,advancements have been made with the intention of improving the residence time or permeation of the drug in the ocular region.Poor bioavailability of topically administered drugs is the major issue pertaining to ocular drug delivery.Several efforts have been made towards improving precorneal residence time and corneal penetration,e.g.iontophoresis,prodrugs and ionpairing,etc.Prodrug approach(chemical approach)has been explored by the formulation scientists to optimize the physicochemical and biochemical properties of drug molecules for improving ocular bioavailability.Formulation of ocular prodrugs is a challenging task as they should exhibit optimum chemical stability as well as enzymatic liability so that they are converted into parent drug after administration at the desired pace.This review will encompass the concept of derivatization and recent academic and industrial advancements in the field of ocular prodrugs.The progression in prodrug designing holds a potential future for ophthalmic drug delivery.

Determination of hydrophilic–lipophilic balance value and emulsion properties of sacha inchi oil

Objective: To determine hydrophilic–lipophilic balance(HLB) value, stability of formulate emulsion and properties of sacha inchi oil.Methods: The physiochemical characteristics of sacha inchi oil were first investigated.Free radical scavenging property was studied by DPPH assay. HLB value of sacha inchi oil was experimentally determined by preparing the emulsion using emulsifiers at different HLB value. Sacha inchi oil emulsion was prepared using the obtained HLB and its stability was conducted by centrifugation, temperature cycling, and accelerated stability test. The efficiency of the prepared emulsion was clinically investigated by 15 volunteers. The primary skin irritation was performed using closed patch test. Subjective sensory assessment was evaluated by using 5-point hedonic scale method.Results: Peroxide value of sacha inchi oil was 18.40 meq O2/kg oil and acid value was1.86 KOH/g oil. The major fatty acids are omega-3(44%), omega-6(35%) and omega-9(9%). The vitamin E content was 226 mg/100 g oil. Moreover, sacha inchi oil(167 ppm)and its emulsion showed 85% and 89% DPPH inhibition, respectively. The experimental HLB value of sacha inchi oil was 8.5. The sacha inchi oil emulsion exhibited good stability after stability test. The emulsion was classified as non-irritant after tested by primary skin irritation method. The skin hydration value significantly increased from38.59 to 45.21(P < 0.05) after applying sacha inchi oil emulsion for 1 month and the overall product satisfaction of volunteers after use was with score of 4.2.Conclusions: This work provides information on HLB value and emulsion properties of sacha inchi oil which is useful for cosmetic and pharmaceutical application.

Quantum Chemistry Prediction of Molecular Lipophilicity Using Semi-Empirical AM1 and <i>Ab Initio</i>HF/6-311++G Levels

Reliable prediction of lipophilicity in organic compounds involves molecular descriptors determination. In this work, the lipophilicity of a set of twenty-three molecules has been determined using up to eleven quantum various descriptors calculated by means of quantum chemistry methods. According to Quantitative Structure Property Relationship (QSPR) methods, a first set of fourteen molecules was used as training set whereas a second set of nine molecules was used as test set. Calculations made at AM1 and HF/6-311++G theories levels have led to establish a QSPR relation able to predict molecular lipophilicity with over 95% confidence.

Antioxidant Capacity and Total Phenol Content of Commonly Consumed Indigenous Foods of Asian Tropical Regions

In order to screen the antioxidant capacity of commonly consumed indigenous foods of tropical region, vegetables, fruits, tea, oil seeds, legumes, spices and cereal were analyzed. Among the vegetables, green chili showed the highest total oxygen radical absorbance capacity （ORACFL） and lipophilic ORAC （L-ORACFL）; whereas, bean showed highest hydrophilic ORAC （H-ORACFL） content. The H-ORACFL of vegetable samples varied between 2.26 to 23.08 ~tmol of Trolox equivalent （TE）/g of fresh weight （FW） and L-ORACFL content widely varied from 0.20 （sweet pumpkin） to 16.95 （green chili）. The range of H-ORACFL values of fruits showed large variation （0.45-178 Ixmol of TE/g FW）. All four different types of tea showed high H-ORACFL （1,295.84-2,709.11 lamol of TE/g）, in contrast to negligible amount of L-ORACFL. In legumes, H-ORACFL content ranged from 16.22 to 140.54; whereas, L-ORACFL ranged from 4.43 to 25.78. Porso millets showed higher L-ORACFL value （19.4） as compared to H-ORACFL （0.8）. In case of spices, L-ORACFL content varied from 29.75 ± 0.00 to 1,575.24 ± 39.63, which is considerably higher as compared to H-ORACFL （61.68 ± 1.71 to 272.82± 1.05） content. Comparatively, spices showed much higher H-ORACFL values as compared to fruits analyzed. In case of selective vegetables, fruits and tea samples, the total phenol content was highly correlated with the H-ORACFL content.

Corn cob modified by lauric acid and ethanediol for emulsified oil adsorption

Corn cob is a naturally renewable material with developed micropore and hydrophobic characteristics, which enables it to show good oil adsorption capacity. In order to improve oil adsorption capacity, corn cob was modified with lauric acid and ethanediol. The structure of raw and modified corn cob was investigated using Fourier transform infrared(FTIR) spectroscopy, scanning electron microscopy(SEM), Brunauer-Emmett-Teller(BET) method, thermogravimetric analysis(TGA) and Ze Ta potential analyzer. The effects of p H level, adsorption time, adsorbent dosage, and initial oil concentration on oil absorbency of corn cob were studied. The results indicate that the modification significantly improved the lipophilicity of corn cob, making the modified corn cob with much better adsorption capacity on oil absorbency. Compared with raw corn cob, the maximum saturated adsorption capacity of modified corn cob is 16.52 mg/g at p H 5, and the increasing percentage is found to be 141%, which indicates that the modification causes a better adsorption capacity for oil removal. In addition, due to high oil adsorption capacity, affordable price and low secondary pollution, the modified corn cob could be considered promising alternative for the traditional oil adsorbent to clean up the emulsified oily water.

Evaluation of CC2 as a Decontaminant in Various Hydrophilicand Lipophilic Formulations Against Sulphur Mustard

Objective To evaluate CC2 (N, N’-dichloro-bis [2, 4, 6-trichlorophenyl] urea) invarious hydrophilic and lipophilic formulations as a personnel decontaminant for sulphurmustard (SM). Methods Twenty percent of CC2 was prepared as a suspension or ointmentwith various chemical agents and its stability was evaluated by active chlorine assay. Theefficacy was evaluated in mice by recording the mortality after applying 29 LD50 of SM (LD50 =8.1 mg/kg dermally) and decontaminating it after 2 min with 200 mg of the formulation.Studies were also carried out with 10% and 20% CC2 in acacia and hydroxypropyl cellulose,and the suspensions were stored in polyethylene containers. The stability of the suspensionswas evaluated by active chlorine assay. The efficacy was evaluated by recording themortality after applying 29 LD50 of SM in mice and 12 LD50 of SM in rats (LD50 = 2.4 mg/kgdermally), and decontaminating it with the formulations. LD50 by different routes andprimary skin irritation test of CC2 were also carried out. Results CC2 reacted with peanutoil and neem oil, and was unstable in povidone iodine and Fuller’s earth. Good stability wasachieved with petroleum jelly, honey, polyvinyl pyrrolidone, calamine lotion, acacia andhydroxypropyl cellulose. Though CC2 was stable in lipophilic formulations, it did notprotect the animals. The hydrophilic formulations particularly acacia and hydroxypropylcellulose gave very good protection and was stable in the polyethylene containers for aperiod of 1 year. The efficacy of 20% CC2 was better than 10% CC2. The oral and dermalLD50 of CC2 was found to be above 5.0 g/kg. CC2 was also found to be nonirritant.Conclusion Twenty percent of CC2 in hydroxypropyl cellulose is better with respect tostability, efficacy and ease of decontamination. CC2 is also a safe chemical.

Spatial variation of lipophilic marine algal toxins and its relationship with physicochemical parameters in spring in Laizhou Bay,China

Lipophilic marine algal toxins(LMATs)are produced by some toxigenic microalgae,which pose a serious threat to marine ecosystem and even human health.The occurrence and environmental control factors of LMATs in the surface seawater and phytoplankton in spring in Laizhou Bay in which Huanghe(Yellow)River estuary is included,in Shandong,East China were investigated.Okadaic acid(OA),pectenotoxin-2(PTX2),dinophysistoxin-1(DTX1),pectenotoxin-2 seco acid(PTX2 SA),DTX2,7-epi-PTX2 SA,PTX11,and 13-desmethyl spirolide C(SPX1)were detected from the surface seawater samples,and PTX2,7-epi-PTX2 SA,OA,DTX2,DTX1,PTX2 SA,and PTX11 were discovered in the phytoplankton samples showed a decreasing trend.The concentrations of∑LMATs in the seawater and phytoplankton ranged 2.03-74.38 ng/L on average of 13.72 ng/L and 0.98-479.27 pg/L on average of 50.20 pg/L,respectively.The joint influence of terrigenous input and internal circulation could promote the growth,toxin production,and toxin release of toxin-producing algae,leading to a higher content of LMATs in the bay nearby the Huanghe River estuary in both seawater and phytoplankton.The concentration of LMATs in spring was higher than that in summer,showing obvious seasonal variation.In addition,no significant correlation between most of the physiochemical parameters and LMAT contents in seawater was revealed by correlation analysis except for the positive correlation between DTX2 and chlorophyll a,OA and NH4-N.However,the increase of dissolved inorganic nitrogen content in seawater could enhance the production of OA,DTX1,and DTX2 in phytoplankton due probably to that the inorganic N input could benefit the growth and stimulate toxin production of toxin-producing algae.The result also proved that some PTX2 may be originated from Procentrum spp.and OA,DTXs and part of PTX2 may be originated from Dinophysis spp.

Acid-base and lipophilic properties of peptide nucleic acid derivatives

The first combined experimental and theoretical study on the ionization and lipophilic properties of peptide nucleic acid(PNA)derivatives,including eleven PNA monomers and two PNA decamers,is described.The acidity constants(pKa)of individual acidic and basic centers of PNA monomers were measured by automated potentiometric pH titrations in water/methanol solution,and these values were found to be in agreement with those obtained by MoKa software.These results indicate that single nucleobases do not change their pKa values when included in PNA monomers and oligomers.In addition,immobilized artificial membrane chromatography was employed to evaluate the lipophilic properties of PNA monomers and oligomers,which showed the PNA derivatives had poor affinity towards membrane phospholipids,and confirmed their scarce cell penetrating ability.Overall,our study not only is of potential relevance to evaluate the pharmacokinetic properties of PNA,but also constitutes a reliable basis to properly modify PNA to obtain mimics with enhanced cell penetration properties.

A new lipophilic monosaccharide from Erigeron annuus

A new lipophilic monosaccharide, erigearide A （1）, was isolated from the aerial parts of Erigeron annuus （Lima.） Pers. Its structure was elucidated by analysis of spectroscopic evidence.

Screening for lipophilic marine toxins and their potential producers in coastal waters of Weihai in autumn,2020

Lipophilic marine toxins(LMTs)produced by some microalgae in the sea could accumulate in shellfish and pose potential threats to the health of seafood consumers.Phytoplankton and shellfish samples were collected from coastal waters of Weihai in Shandong Peninsula,China in autumn,2020,and screened for lipophilic marine toxins and their potential producers using liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis and high throughput sequencing of partial DNA(V4 region of the 18S rRNA gene)extracted from phytoplankton.Pectenotoxin-2(PTX2),trace amounts of azaspiracid(AZA1 or AZA40),and 13-desmethyl spirolide C(13-DesMe-C)were detected in phytoplankton samples,while PTX2 and gymnodimine(GYM)were detected in shellfish samples.The toxin content in shellfish samples was much lower than the regulatory limit or values reported previously.Results suggest that lipophilic marine toxins should have low risk in coastal waters of Weihai in autumn.Based on the data of high throughput sequencing,the OTUs were assigned to 5 identified species of Alexandrium,including A.ostenfeldii capable of producing 13-DesMe-C and GYM.Two OTUs were found closely related to the toxic species in genus Dinophysis,but it is impossible to assign them to any identified species due to the low resolving power of the V4 region for Dinophysis.The OTUs could not be assigned to any identified species in the genus Azadinium,suggesting the existence of unidentified species in this region.