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1.
Ecol Evol ; 14(6): e11536, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38932952

ABSTRACT

In recent years, illegal felling of and damage to the incense tree Aquilaria sinensis (Lour.) Spreng. have been reported in Hong Kong. Their native populations are under increasingly severe threat. Therefore, the development of a standard and efficient method to classify and document wounds on vulnerable trees is urgently needed for conservation purposes. In this study, photogrammetry was used to document wounds in A. sinensis through 3D modeling. A total of 752 wound records from 484 individual A. sinensis trees from Hong Kong were included to establish a new wound classification system. Our major findings include a novel standardized procedure for photogrammetric documentation and a wound classification system. The results of this study will facilitate A. sinensis conservation, by enhancing wound documentation and information transfer to law enforcement and education.

2.
Bioresour Technol ; 399: 130636, 2024 May.
Article in English | MEDLINE | ID: mdl-38548032

ABSTRACT

Biofuel production from microalgae has been greatly restricted by low biomass productivity and long-term photosynthetic efficacy. Here, a novel strategy for selecting high-growing, stress-resistant algal strains with high photosynthetic capacity was proposed based on biocompatible extracellular polymeric substances (EPS) probes with aggregation-induced emission (AIE) properties. Specifically, AIE active EPS probes were synthesized for in-situ long-term monitoring of the EPS productivity at different algal growth stages. By coupling the AIE-based fluorescent techniques, algal cells were classified into four diverse populations based on their chlorophyll and EPS signals. Mechanistic studies on the sorted algal cells revealed their remarkable stress resistance and high expression of cell division, biopolymer production and photosynthesis-related genes. The sorted and subcultured algal cells consistently exhibited relatively higher growth rates and photosynthetic capacities, resulting in an increased (1.2 to 1.8-fold) algal biomass production, chlorophyll, and lipids. This study can potentially open new strategies to boost microalgal-based biofuel production.


Subject(s)
Chlamydomonas reinhardtii , Microalgae , Chlamydomonas reinhardtii/genetics , Chlamydomonas reinhardtii/metabolism , Biofuels , Extracellular Polymeric Substance Matrix/metabolism , Bioprospecting , Chlorophyll/metabolism , Microalgae/metabolism
3.
Surg Endosc ; 38(5): 2577-2592, 2024 May.
Article in English | MEDLINE | ID: mdl-38498212

ABSTRACT

INTRODUCTION: There is growing evidence that the use of robotic-assisted surgery (RAS) in colorectal cancer resections is associated with improved short-term outcomes when compared to laparoscopic surgery (LS) or open surgery (OS), possibly through a reduced systemic inflammatory response (SIR). Serum C-reactive protein (CRP) is a sensitive SIR biomarker and its utility in the early identification of post-operative complications has been validated in a variety of surgical procedures. There remains a paucity of studies characterising post-operative SIR in RAS. METHODS: Retrospective study of a prospectively collected database of consecutive patients undergoing OS, LS and RAS for left-sided and rectal cancer in a single high-volume unit. Patient and disease characteristics, post-operative CRP levels, and clinical outcomes were reviewed, and their relationships explored within binary logistic regression and propensity scores matched models. RESULTS: A total of 1031 patients were included (483 OS, 376 LS, and 172 RAS). RAS and LS were associated with lower CRP levels across the first 4 post-operative days (p < 0.001) as well as reduced complications and length of stay compared to OS in unadjusted analyses. In binary logistic regression models, RAS was independently associated with lower CRP levels at Day 3 post-operatively (OR 0.35, 95% CI 0.21-0.59, p < 0.001) and a reduction in the rate of all complications (OR 0.39, 95% CI 0.26-0.56, p < 0.001) and major complications (OR 0.5, 95% CI 0.26-0.95, p = 0.036). Within a propensity scores matched model comparing LS versus RAS specifically, RAS was associated with lower post-operative CRP levels in the first two post-operative days, a lower proportion of patients with a CRP ≥ 150 mg/L at Day 3 (20.9% versus 30.5%, p = 0.036) and a lower rate of all complications (34.7% versus 46.7%, p = 0.033). CONCLUSIONS: The present observational study shows that an RAS approach was associated with lower postoperative SIR, and a better postoperative complications profile.


Subject(s)
C-Reactive Protein , Postoperative Complications , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/methods , Female , Male , Retrospective Studies , Aged , Middle Aged , C-Reactive Protein/metabolism , C-Reactive Protein/analysis , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Laparoscopy/methods , Rectal Neoplasms/surgery , Treatment Outcome , Colectomy/methods , Proctectomy/methods , Proctectomy/adverse effects , Length of Stay/statistics & numerical data , Stress, Physiological
4.
Adv Colloid Interface Sci ; 325: 103094, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38359673

ABSTRACT

Nanoparticles as cancer therapeutic carrier fail in clinical translation due to complex biological environments in vivo consisting of electrolytes and proteins which render nanoparticle aggregation and unable to reach action site. This review identifies the desirable characteristics of nanoparticles and their constituent materials that prevent aggregation from site of administration (oral, lung, injection) to target site. Oral nanoparticles should ideally be 75-100 nm whereas the size of pulmonary nanoparticles minimally affects their aggregation. Nanoparticles generally should carry excess negative surface charges particularly in fasting state and exert steric hindrance through surface decoration with citrate, anionic surfactants and large polymeric chains (polyethylene glycol and polyvinylpyrrolidone) to prevent aggregation. Anionic as well as cationic nanoparticles are both predisposed to protein corona formation as a function of biological protein isoelectric points. Their nanoparticulate surface composition as such should confer hydrophilicity or steric hindrance to evade protein corona formation or its formation should translate into steric hindrance or surface negative charges to prevent further aggregation. Unexpectedly, smaller and cationic nanoparticles are less prone to aggregation at cancer cell interface favoring endocytosis whereas aggregation is essential to enable nanoparticles retention and subsequent cancer cell uptake in tumor microenvironment. Present studies are largely conducted in vitro with simplified simulated biological media. Future aggregation assessment of nanoparticles in biological fluids that mimic that of patients is imperative to address conflicting materials and designs required as a function of body sites in order to realize the future clinical benefits.


Subject(s)
Nanoparticles , Neoplasms , Protein Corona , Humans , Protein Corona/metabolism , Nanoparticles/metabolism , Polymers , Polyethylene Glycols , Neoplasms/drug therapy , Particle Size , Tumor Microenvironment
5.
Phytomedicine ; 123: 155229, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38006804

ABSTRACT

BACKGROUND: Triphala (TLP), as a Chinese Tibetan medicine composing of Emblica officinalis, Terminalia chebula and Terminalia bellirica (1.2:1.5:1), exhibited hepatoprotective, hypolipidemic and gut microbiota modulatory effects. Nonetheless, its roles in prevention of high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and the related mechanistic insights involving the interplay of gut microbiota and hepatic inflammation are not known. PURPOSE: The present study seeks to determine if TLP would prevent HFD-induced NAFLD in vivo and its underlying mechanisms from the perspectives of gut microbiota, metabolites, and hepatic inflammation. METHODS: TLP was subjected to extraction and chemo-profiling, and in vivo evaluation in HFD-fed rats on hepatic lipid and inflammation, intestinal microbiota, short-chain fatty acids (SCFAs) and permeability, and body weight and fat content profiles. RESULTS: The TLP was primarily constituted of gallic acid, corilagin and chebulagic acid. Orally administered HFD-fed rats with TLP were characterized by the growth of Ligilactobacillus and Akkermansia, and SCFAs (acetic/propionic/butyric acid) secretion which led to increased claudin-1 and zonula occludens-1 expression that reduced the mucosal permeability to migration of lipopolysaccharides (LPS) into blood and liver. Coupling with hepatic cholesterol and triglyceride lowering actions, the TLP mitigated both inflammatory (ALT, AST, IL-1ß, IL-6 and TNF-α) and pro-inflammatory (TLR4, MYD88 and NF-κB P65) activities of liver, and sequel to histopathological development of NAFLD in a dose-dependent fashion. CONCLUSION: TLP is promisingly an effective therapy to prevent NAFLD through modulating gut microbiota, mucosal permeability and SCFAs secretion with liver fat and inflammatory responses.


Subject(s)
Non-alcoholic Fatty Liver Disease , Plant Extracts , Rats , Animals , Mice , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/prevention & control , Non-alcoholic Fatty Liver Disease/metabolism , Medicine, Tibetan Traditional , Liver , Inflammation/metabolism , Diet, High-Fat/adverse effects , China , Mice, Inbred C57BL
6.
ACS Nano ; 17(22): 22240-22258, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37966480

ABSTRACT

Sorafenib, a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), has been shown to be a potent ferroptosis inducer in HCC. However, we found that there was a lower level of ferroptosis in sorafenib-resistant HCC samples than in sorafenib-sensitive HCC samples, suggesting that sorafenib resistance in HCC may be a result of ferroptosis suppression. Recent reports have shown that long noncoding RNAs (lncRNAs) are involved in programmed cell death (PCD), including apoptosis and ferroptosis. This study aimed to investigate the roles and underlying molecular mechanisms of lncRNAs in sorafenib-induced ferroptosis in HCC cells. Using lncRNA sequencing, we identified a ferroptosis-related lncRNA, URB1-antisense RNA 1 (AS1), which was highly expressed in sorafenib-resistant HCC samples and predicted poor survival in HCC. Furthermore, URB1-AS1 mitigates sorafenib-induced ferroptosis by inducing ferritin phase separation and reducing the cellular free iron content. Hypoxia inducible factor (HIF)-1α was identified as a key factor promoting URB1-AS1 expression in sorafenib-resistant HCC cells. Notably, we found that specifically inhibiting the expression of URB1-AS1 with N-acetylgalactosamine (GalNAc)-small interfering (si)URB1-AS1 successfully enhanced the sensitivity of HCC cells to sorafenib in an in vivo tumor model. Our study uncovered a critical role for URB1-AS1 in the repression of ferroptosis, suggesting URB1-AS1 targeting may represent a potential approach to overcome sorafenib resistance in HCC.


Subject(s)
Carcinoma, Hepatocellular , Ferroptosis , Liver Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Sorafenib/pharmacology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , RNA, Antisense , Ferritins/metabolism , MicroRNAs/genetics , Cell Line, Tumor , RNA, Small Interfering/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , Nuclear Proteins/genetics
7.
JCEM Case Rep ; 1(1): luac008, 2023 Jan.
Article in English | MEDLINE | ID: mdl-37908265

ABSTRACT

This is a unique case of ectopic adrenocorticotropic hormone (ACTH)-secreting mediastinal neuroendocrine tumor, presumably thymic in origin, with suspected lung metastasis in a 61-year-old man who was successfully managed with long-term metyrapone alone. He presented with severe hypokalemia and hypertension, complicated with psychosis and vertebral collapse. He survived through a complicated course of pulseless ventricular tachycardia arrest and a severe Cushing storm due to drug nonadherence. For 3 years since diagnosis, he remained stable on metyrapone, and was able to achieve biochemical eucortisolism, with normalization of ACTH and cortisol levels. In addition, his tumor was reduced in size and the suspicious lung metastasis regressed.

8.
Asian J Pharm Sci ; 18(5): 100848, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37881796

ABSTRACT

Virus-capsid mimicking mucus-permeable nanoparticles are promising oral insulin carriers which surmount intestinal mucus barrier. However, the impact of different virus-capsid mimicking structure remains unexplored. In this study, utilizing biotin grafted chitosan as the main skeleton, virus-mimicking nanoparticles endowed with biologic-shell (streptavidin coverage) and polymeric-shell (hyaluronic acid/alginate coating) were designed with insulin as a model drug by self-assembly processes. It was demonstrated that biologic-shell mimicking nanoparticles exhibited a higher intestinal trans-mucus (>80%, 10 min) and transmucosal penetration efficiency (1.6-2.2-fold improvement) than polymeric-shell counterparts. Uptake mechanism studies revealed caveolae-mediated endocytosis was responsible for the absorption of biologic-shell mimicking nanoparticles whereas polymeric-shell mimicking nanoparticles were characterized by clathrin-mediated pathway with anticipated lysosomal insulin digestion. Further, in vivo hypoglycemic study indicated that the improved effect of regulating blood sugar levels was virus-capsid structure dependent out of which biologic-shell mimicking nanoparticles presented the best performance (5.1%). Although the findings of this study are encouraging, much more work is required to meet the standards of clinical translation. Taken together, we highlight the external structural dependence of virus-capsid mimicking nanoparticles on the muco-penetrating and uptake mechanism of enterocytes that in turn affecting their in vivo absorption, which should be pondered when engineering virus-mimicking nanoparticles for oral insulin delivery.

9.
ISME J ; 17(12): 2303-2312, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37875603

ABSTRACT

Marine biofilms are complex communities of microorganisms that play a crucial ecological role in oceans. Although prokaryotes are the dominant members of these biofilms, little is known about their interactions with viruses. By analysing publicly available and newly sequenced metagenomic data, we identified 2446 virus-prokaryote connections in 84 marine biofilms. Most of these connections were between the bacteriophages in the Uroviricota phylum and the bacteria of Proteobacteria, Cyanobacteria and Bacteroidota. The network of virus-host pairs is complex; a single virus can infect multiple prokaryotic populations or a single prokaryote is susceptible to several viral populations. Analysis of genomes of paired prokaryotes and viruses revealed the presence of 425 putative auxiliary metabolic genes (AMGs), 239 viral genes related to restriction-modification (RM) systems and 38,538 prokaryotic anti-viral defence-related genes involved in 15 defence systems. Transcriptomic evidence from newly established biofilms revealed the expression of viral genes, including AMGs and RM, and prokaryotic defence systems, indicating the active interplay between viruses and prokaryotes. A comparison between biofilms and seawater showed that biofilm prokaryotes have more abundant defence genes than seawater prokaryotes, and the defence gene composition differs between biofilms and the surrounding seawater. Overall, our study unveiled active viruses in natural biofilms and their complex interplay with prokaryotes, which may result in the blooming of defence strategists in biofilms. The detachment of bloomed defence strategists may reduce the infectivity of viruses in seawater and result in the emergence of a novel role of marine biofilms.


Subject(s)
Cyanobacteria , Viruses , Transcriptome , Viruses/genetics , Seawater/microbiology , Genomics , Cyanobacteria/genetics , Biofilms
10.
Int J Biol Macromol ; 253(Pt 4): 126991, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37739286

ABSTRACT

Solid particles ≤5 µm are essential to allow lower lung deposition and macrophage phagocytosis of anti-tubercular drugs. Decorating liquid nanoemulsion of anti-tubercular drug with macrophage-specific chitosan and chitosan-folate conjugate and spray drying the nanoemulsion with lactose produced oversized solid particles due to polysaccharide binding effects. This study designed solid nanoemulsion using lactose as the primary solid carrier and explored additives and spray-drying variables to reduce the binding and particle growth effects of chitosan. Deposition of magnesium stearate on lactose negated chitosan-inducible excessive lactose-liquid nanoemulsion binding and solid particle growth. Moderating the adhesion of chitosan-decorated liquid nanoemulsion onto lactose produced smooth-surface solid microparticles (size: 5.45 ± 0.26 µm; roughness: ∼80 nm) with heterogeneous size (span: 1.87 ± 1.21) through plasticization of constituent materials of nanoemulsion and lactose involving OH/N-H, C-H, CONH and/or COO moieties. Smaller solid particles could attach onto the larger particles with minimal steric hindrance by smooth surfaces. Together with round solid particulate structures (circularity: 0.919 ± 0.002), good pulmonary inhalation beneficial for treatment of pulmonary tuberculosis as well as other diseases is conferred.


Subject(s)
Chitosan , Chitosan/chemistry , Lactose/chemistry , Drug Carriers/chemistry , Lung/metabolism , Administration, Inhalation , Particle Size , Powders/metabolism
11.
Biotechnol Adv ; 67: 108200, 2023 10.
Article in English | MEDLINE | ID: mdl-37331671

ABSTRACT

Chitosan is a biotechnological derivative of chitin receiving a widespread pharmaceutical and biomedical applications. It can be used to encapsulate and deliver cancer therapeutics with inherent pH-dependent solubility to confer drug targeting at tumour microenvironment and anti-cancer activity synergizing cancer cytotoxic drug actions. To further reduce the off-target and by-stander adverse effects of drugs, a high targeted drug delivery efficiency at the lowest possible drug doses is clinically required. The chitosan has been functionalized with covalent conjugates or complexes and processed into nanoparticles to encapsulate and control drug release, to avoid premature drug clearance, to deliver drugs passively and actively to cancer site at tissue, cell or subcellular levels, and to promote cancer cell uptake of nanoparticles through membrane permeabilization at higher specificity and scale. Nanomedicine developed using functionalized chitosan translates to significant preclinical improvements. Future challenges related to nanotoxicity, manufacturability, selection precision of conjugates and complexes as a function of cancer omics and their biological responses from administration site to cancer target need critical assessments.


Subject(s)
Chitosan , Nanoparticles , Neoplasms , Humans , Chitosan/therapeutic use , Drug Carriers , Drug Delivery Systems , Neoplasms/metabolism , Nanoparticles/therapeutic use , Tumor Microenvironment
12.
Nat Commun ; 14(1): 2861, 2023 05 19.
Article in English | MEDLINE | ID: mdl-37208334

ABSTRACT

Targetable drivers governing 5-fluorouracil and cisplatin (5FU + CDDP) resistance remain elusive due to the paucity of physiologically and therapeutically relevant models. Here, we establish 5FU + CDDP resistant intestinal subtype GC patient-derived organoid lines. JAK/STAT signaling and its downstream, adenosine deaminases acting on RNA 1 (ADAR1), are shown to be concomitantly upregulated in the resistant lines. ADAR1 confers chemoresistance and self-renewal in an RNA editing-dependent manner. WES coupled with RNA-seq identify enrichment of hyper-edited lipid metabolism genes in the resistant lines. Mechanistically, ADAR1-mediated A-to-I editing on 3'UTR of stearoyl-CoA desaturase (SCD1) increases binding of KH domain-containing, RNA-binding, signal transduction-associated 1 (KHDRBS1), thereby augmenting SCD1 mRNA stability. Consequently, SCD1 facilitates lipid droplet formation to alleviate chemotherapy-induced ER stress and enhances self-renewal through increasing ß-catenin expression. Pharmacological inhibition of SCD1 abrogates chemoresistance and tumor-initiating cell frequency. Clinically, high proteomic level of ADAR1 and SCD1, or high SCD1 editing/ADAR1 mRNA signature score predicts a worse prognosis. Together, we unveil a potential target to circumvent chemoresistance.


Subject(s)
Adenosine Deaminase , Drug Resistance, Neoplasm , Stearoyl-CoA Desaturase , Stomach Neoplasms , Humans , Adaptor Proteins, Signal Transducing/metabolism , Adenosine Deaminase/genetics , Adenosine Deaminase/metabolism , Cisplatin/pharmacology , Cisplatin/therapeutic use , Cisplatin/metabolism , DNA-Binding Proteins/metabolism , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Proteomics , RNA/metabolism , RNA Editing , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Stearoyl-CoA Desaturase/genetics , Stearoyl-CoA Desaturase/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics
13.
Asian J Pharm Sci ; 18(2): 100794, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37035131

ABSTRACT

Nanoscale medicine confers passive and active targeting potential. The development of nanomedicine is however met with processing, handling and administration hurdles. Excessive solid nanoparticle aggregation and caking result in low product yield, poor particle flowability and inefficient drug administration. These are overcome by converting the nanoparticles into a microscale dosage form via agglomeration or compaction techniques. Agglomeration and compaction nonetheless predispose the nanoparticles to risks of losing their nanogeometry, surface composition or chemistry being altered and negating biological performance. This study reviews risk factors faced during agglomeration and compaction that could result in these changes to nanoparticles. The potential risk factors pertain to materials choice in nanoparticle and microscale dosage form development, and their interplay effects with process temperature, physical forces and environmental stresses. To render the physicochemical and biological behaviour of the nanoparticles unaffected by agglomeration or compaction, modes to modulate the interplay effects of material and formulation with processing and environment variables are discussed.

14.
J Hazard Mater ; 445: 130599, 2023 03 05.
Article in English | MEDLINE | ID: mdl-37055998

ABSTRACT

Silver nanoparticles (AgNPs), which have been used extensively in consuming products and eventually released into the natural environment, have aroused concerns recently because of their potentially harmful effects on human beings following various routes of exposure. As the liver is one of the largest accumulation and deposition sites of circulatory AgNPs, it is important to evaluate the hepatotoxicity induced by AgNPs. However, the acting mechanisms of AgNPs-induced hepatotoxicity are still elusive to a great extent. Herein, we investigated the hepatotoxic effects of AgNPs using a comparative proteomics approach. First, we evaluated the cytotoxicity of different-sized AgNPs and found that the cancerous liver cells were generally more sensitive than the normal liver cells. Next, proteomics results suggested that HepG2 and L02 cells showed distinct adaptive responses upon AgNPs exposure. HepG2 cells respond to stresses by adapting energy metabolism, upregulating metallothionein expression and increasing the expression of antioxidants, while L02 cells protect themselves by increasing DNA repair and macro-autophagy. Besides, mitochondrial ROS has been identified as one of the causes of AgNPs-induced hepatotoxicity. Collectively, our results revealed that hepatic cancer cells and normal cells cope with AgNPs in notably different pathways, providing new insights into mechanisms underlying AgNPs-induced hepatotoxicity. DATA AVAILABILITY: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (Deutsch et al. (2020)) via the PRIDE (Perez-Riverol et al. (2019)) partner repository with the dataset identifier PXD029511.


Subject(s)
Chemical and Drug Induced Liver Injury , Metal Nanoparticles , Humans , Silver/chemistry , Reactive Oxygen Species/metabolism , Proteomics/methods , Metal Nanoparticles/toxicity , Hepatocytes , Chemical and Drug Induced Liver Injury/metabolism
15.
Int J Biol Macromol ; 241: 124506, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37085071

ABSTRACT

Starch is a polysaccharide with varying amylose-to-amylopectin ratios as a function of its biological sources. It is characterized by low shear stress resistance, poor aqueous/organic solubility and gastrointestinal digestibility which limit its ease of processing and functionality display as an oral drug delivery vehicle. Modulation of starch composition through genetic engineering primarily alters amylose-to-amylopectin ratio. Greater molecular properties changes require chemical and enzymatic modifications of starch. Acetylation reduces water solubility and enzymatic digestibility of starch. Carboxymethylation turns starch acid-insoluble and aggregative at low pHs. The summative effects are sustaining drug release in the upper gut. Acid-insoluble carboxymethylated starch can be aminated to provide an ionic character essential for hydrogel formation which further reduces its drug release. Ionic starch can coacervate with oppositely charged starch, non-starch polyelectrolyte or drug into insoluble, controlled-release complexes. Enzymatically debranched and resistant starch has a small molecular size which confers chain aggregation into a helical hydrogel network that traps the drug molecules, protecting them from biodegradation. The modified starch has been used to modulate the intestinal/colon-specific or controlled systemic delivery of oral small molecule drugs and macromolecular therapeutics. This review highlights synthesis aspects of starch and starch derivatives, and their outcomes and challenges of applications in oral drug delivery.


Subject(s)
Amylopectin , Starch , Starch/chemistry , Amylopectin/chemistry , Amylose/chemistry , Drug Delivery Systems , Solubility
16.
Hepatology ; 78(6): 1711-1726, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-36630996

ABSTRACT

BACKGROUND AND AIMS: HCC is an aggressive disease with poor clinical outcome. Understanding the mechanisms that drive cancer stemness, which we now know is the root cause of therapy failure and tumor recurrence, is fundamental for designing improved therapeutic strategies. This study aims to identify molecular players specific to CD133 + HCC to better design drugs that can precisely interfere with cancer stem cells but not normal stem cell function. APPROACH AND RESULTS: Transcriptome profiling comparison of epithelial-specific "normal" CD133 + cells isolated from fetal and regenerating liver against "HCC" CD133 + cells isolated from proto-oncogene-driven and inflammation-associated HCC revealed preferential overexpression of SERPINA12 in HCC but not fetal and regenerating liver CD133 + cells. SERPINA12 upregulation in HCC is tightly associated with aggressive clinical and stemness features, including survival, tumor stage, cirrhosis, and stemness signatures. Enrichment of SERPINA12 in HCC is mediated by promoter binding of the well-recognized ß-catenin effector TCF7L2 to drive SERPINA12 transcriptional activity. Functional characterization identified a unique and novel role of endogenous SERPINA12 in promoting self-renewal, therapy resistance, and metastatic abilities. Mechanistically, SERPINA12 functioned through binding to GRP78, resulting in a hyperactivated AKT/GSK3ß/ß-catenin signaling cascade, forming a positive feed-forward loop. Intravenous administration of rAAV8-shSERPINA12 sensitized HCC cells to sorafenib and impeded the cancer stem cell subset in an immunocompetent HCC mouse model. CONCLUSIONS: Collectively, our findings revealed that SERPINA12 is preferentially overexpressed in epithelial HCC CD133 + cells and is a key contributor to HCC initiation and progression by driving an AKT/ß-catenin feed-forward loop.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Mice , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , beta Catenin/metabolism , Cell Line, Tumor , Neoplasm Recurrence, Local/pathology , Neoplastic Stem Cells/metabolism , Cell Proliferation
17.
Int J Biol Macromol ; 226: 321-335, 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36502951

ABSTRACT

The anti-hyperpigmentation effect and tyrosinase inhibitory mechanism of cinnamon polysaccharides have not been reported. The current study focused on the extraction of polysaccharides from Cinnamomum cassia bark using microwave-assisted approach and optimization of the extraction process (i.e., microwave power, irradiation time and buffer-to-sample ratio) by Box-Behnken design to obtain a high yield of polysaccharides with high sun protection factor (SPF), anti-hyperpigmentation and antioxidant activities. The extracted pectic-polysaccharides had low molecular weight and degree of esterification. The optimal extraction process had polysaccharides characterized by (a) monophenolase inhibitory activity = 97.5 %; (b) diphenolase inhibitory activity = 99.4 %; (c) ferric reducing antioxidant power = 4.4 mM; (d) SPF = 6.1; (e) yield = 13.7 %. The SPF, tyrosinase inhibitory and antioxidant activities were primarily contributed by the polysaccharides. In conclusion, the polysaccharides from C. cassia could be an alternative therapeutic source for skin hyperpigmentation treatment.


Subject(s)
Antioxidants , Cinnamomum aromaticum , Antioxidants/pharmacology , Microwaves , Monophenol Monooxygenase , Polysaccharides/pharmacology
18.
J Proteome Res ; 22(1): 62-77, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36480915

ABSTRACT

N-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides. We quantified the distributions of intact site-specific glycopeptides in hemagglutinin of A/chicken/Wuxi/0405005/2013 (H7N9) and A/mute swan/Rhode Island/A00325125/2008 (H7N3). Results showed that hemagglutinin for both viruses had complex N-glycans at N22, N38, N240, and N483 but only high-mannose glycans at N411 and, however, that the type and quantities of glycans were distinct between these viruses. Collisional cross section (CCS) provided by the ion mobility spectrometry from the timsTOF Pro MS data differentiated sialylation linkages of the glycopeptides. In summary, timsTOF Pro MS method can quantify intact site-specific glycans for influenza glycoproteins without enrichment and thus facilitate influenza vaccine development and production.


Subject(s)
Influenza A Virus, H7N9 Subtype , Influenza, Human , Humans , Hemagglutinins , Influenza A Virus, H7N3 Subtype/metabolism , Glycoproteins/analysis , Glycopeptides/analysis , Polysaccharides/metabolism
19.
Food Chem ; 409: 135334, 2023 May 30.
Article in English | MEDLINE | ID: mdl-36586266

ABSTRACT

Edible bird's nest (EBN) is a popular and expensive food material. The limited supply and great demand result in the use of adulterants. The authenticity concern is raised due to the lack of appropriate quality markers. Herein, this study aims to provide a specific oligosaccharide marker for rapid EBN authentication. Comparing the benzocaine (ABEE)-labeled saccharide profiles of multiple batches of EBN and adulterants indicates seven unique EBN oligosaccharides. The most abundant one, named BNM001, was selected as a marker and characterized to be Neu5Ac (2-3) Gal by MS and NMR spectra. This new oligosaccharide marker enables a rapid authentication of EBN within 10 min. ABEE labelling of this marker further upgraded the accuracy and sensitivity of the LC-qTOF-MS quantitative analysis. The relative marker content was associated with the quality of EBN products. These results suggest a specific and efficient quality marker for rapid authentication of EBN and related products.


Subject(s)
Birds , Oligosaccharides , Animals , Carbohydrates , Food , Mass Spectrometry
20.
Dev Psychol ; 59(3): 431-441, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36342436

ABSTRACT

Understanding of the complement principle has been proposed as closely related to computational skills, but few studies have investigated their interrelations. The present longitudinal study attempted to clarify the picture by examining their potential cross-lagged relation. Fourth graders (n = 221) in Hong Kong received 3 cognitive assessments at intervals of 6 months, consisting of multiple measures of complement understanding, a nonverbal intelligence test, and a computational skills measure. A random intercept cross-lagged panel model revealed that complement understanding significantly predicted future computational skills, but the reciprocal prediction was nonsignificant. The findings provide empirical evidence supporting the close relation between complement understanding and computational skills and call for future endeavors to examine the interrelations between computational skills and understanding of other arithmetic principles. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Nonoxynol , Humans , Longitudinal Studies , Hong Kong , Mathematics
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