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1.
J Nanobiotechnology ; 22(1): 371, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918805

ABSTRACT

The gut microbiota is one of the essential contributors of the pathogenesis and progress of inflammatory bowel disease (IBD). Compared with first-line drug therapy, probiotic supplementation has emerged as a viable and secure therapeutic approach for managing IBD through the regulation of both the immune system and gut microbiota. Nevertheless, the efficacy of oral probiotic supplements is hindered by their susceptibility to the gastrointestinal barrier, leading to diminished bioavailability and restricted intestinal colonization. Here, we developed a bacteria-microalgae symbiosis system (EcN-SP) for targeted intestinal delivery of probiotics and highly effective treatment of colitis. The utilization of mircroalge Spirulina platensis (SP) as a natural carrier for the probiotic Escherichia coli Nissle 1917 (EcN) demonstrated potential benefits in promoting EcN proliferation, facilitating effective intestinal delivery and colonization. The alterations in the binding affinity of EcN-SP within the gastrointestinal environment, coupled with the distinctive structural properties of the SP carrier, served to overcome gastrointestinal barriers, minimizing transgastric EcN loss and enabling sustained intestinal retention and colonization. The oral administration of EcN-SP could effectively treat IBD by reducing the expression of intestinal inflammatory factors, maintaining the intestinal barrier and regulating the balance of gut microbiota. This probiotic delivery approach is inspired by symbiotic interactions found in nature and offers advantages in terms of feasibility, safety, and efficacy, thus holding significant promise for the management of gastrointestinal disorders.


Subject(s)
Escherichia coli , Gastrointestinal Microbiome , Microalgae , Probiotics , Spirulina , Symbiosis , Animals , Mice , Inflammatory Bowel Diseases/microbiology , Inflammatory Bowel Diseases/therapy , Humans , Colitis , Mice, Inbred C57BL , Male , Drug Delivery Systems/methods
2.
Hum Genomics ; 15(1): 30, 2021 05 25.
Article in English | MEDLINE | ID: mdl-34034810

ABSTRACT

UDP-glucuronosyltransferases (UGTs) are the main phase II drug-metabolizing enzymes mediating the most extensive glucuronidation-binding reaction in the human body. The UGT1A family is involved in more than half of glucuronidation reactions. However, significant differences exist in the distribution of UGT1As in vivo and the expression of UGT1As among individuals, and these differences are related to the occurrence of disease and differences in metabolism. In addition to genetic polymorphisms, there is now interest in the contribution of epigenetics and noncoding RNAs (especially miRNAs) to this differential change. Epigenetics regulates UGT1As pretranscriptionally through DNA methylation and histone modification, and miRNAs are considered the key mechanism of posttranscriptional regulation of UGT1As. Both epigenetic inheritance and miRNAs are involved in the differences in sex expression and in vivo distribution of UGT1As. Moreover, epigenetic changes early in life have been shown to affect gene expression throughout life. Here, we review and summarize the current regulatory role of epigenetics in the UGT1A family and discuss the relationship among epigenetics and UGT1A-related diseases and treatment, with references for future research.


Subject(s)
Epigenesis, Genetic/genetics , Glucuronosyltransferase/genetics , Inactivation, Metabolic/genetics , Glucuronosyltransferase/metabolism , Humans , MicroRNAs/genetics , Multigene Family/genetics
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(7): 792-796, 2022 Jul 15.
Article in Zh | MEDLINE | ID: mdl-35894195

ABSTRACT

OBJECTIVES: To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates. METHODS: A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced. RESULTS: In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05). CONCLUSIONS: UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.


Subject(s)
Glucuronosyltransferase , Hyperbilirubinemia, Neonatal , Asian People/genetics , China , Exons , Glucuronosyltransferase/genetics , Humans , Hyperbilirubinemia, Neonatal/genetics , Infant, Newborn , Mutation
4.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(2): 261-266, 2021 04 25.
Article in English | MEDLINE | ID: mdl-34137228

ABSTRACT

Microalgae is an easy-to-obtain natural biological material with many varieties and abundant natural reserves. Microalgae are rich in natural fluorescein, which can be used as a contrast agent for fluorescence imaging and photoacoustic imaging for medical imaging. With its active surface, microalgae can effectively adsorb functional molecules, metal elements, etc., and have good application prospects in the field of drug delivery. Microalgae can generate oxygen through photosynthesis to increase local oxygen concentration, reverse local hypoxia to enhance the efficacy of hypoxic tumors and promote wound healing. In addition, microalgae have good biocompatibility, and different administration methods have no obvious toxicity. This paper reviews the research progress on the biomedical application of microalgae in bioimaging, drug delivery, hypoxic tumor treatment, wound healing.


Subject(s)
Microalgae , Drug Delivery Systems , Humans , Hypoxia , Oxygen , Wound Healing
5.
Small ; 16(20): e2000819, 2020 05.
Article in English | MEDLINE | ID: mdl-32297465

ABSTRACT

High delivery efficiency, prolonged drug release, and low systemic toxicity are effective weapons for drug delivery systems to win the battle against metastatic breast cancer. Herein, it is shown that Spirulina platensis (S. platensis) can be used as natural carriers to construct a drug-loaded system for targeted delivery and fluorescence imaging-guided chemotherapy on lung metastasis of breast cancer. The chemotherapeutic doxorubicin (DOX) is loaded into S. platensis (SP) via only one facile step to fabricate the DOX-loaded SP (SP@DOX), which exhibits ultrahigh drug loading efficiency and PH-responsive drug sustained release. The rich chlorophyll endows SP@DOX excellent fluorescence imaging capability for noninvasive tracking and real-time monitoring in vivo. Moreover, the micrometer-sized and spiral-shaped SP carriers enable the as-prepared SP@DOX to passively target the lungs and result in a significantly enhanced therapeutic efficacy on lung metastasis of 4T1 breast cancer. Finally, the undelivered carriers can be biodegraded through renal clearance without notable toxicity. The SP@DOX described here presents a novel biohybrid strategy for targeted drug delivery and effective treatment on cancer metastasis.


Subject(s)
Breast Neoplasms , Lung Neoplasms , Microalgae , Nanoparticles , Breast Neoplasms/drug therapy , Cell Line, Tumor , Doxorubicin/therapeutic use , Drug Carriers , Drug Delivery Systems , Drug Liberation , Female , Humans , Lung Neoplasms/drug therapy , Spirulina
6.
Pediatr Res ; 88(6): 940-944, 2020 12.
Article in English | MEDLINE | ID: mdl-32126570

ABSTRACT

BACKGROUND: To investigate the relationship between unexplained indirect hyperbilirubinemia of Vietnamese newborns and the polymorphism of the promoter TATA box and exon 1 of bilirubin uridine diphosphate glucuronosyltransferase (UGT1A1) gene. METHODS: A total of 149 neonates were divided into the hyperbilirubinemia group (n = 99) and control group (n = 50). The gene polymorphisms of UGT1A1 gene in the two groups were detected by PCR and direct sequencing, which revealed the relationship between UGT1A1 polymorphism with neonatal hyperbilirubinemia of neonates. The types of UGT1A1 polymorphism in the hyperbilirubinemia group and the peak total serum bilirubin (PSB) levels with different genotypes were observed. RESULTS: (1) (TA)7 insertion mutation, 211G>A, 189C>T, 190G>A, 378C>T and 686C>A were detected. (2) The allele frequency of 211G>A allele mutation was significantly different between the two groups (p < 0.05). (3) Logistic regression analysis showed that homozygosity and heterozygosity of 211G>A were both significantly associated with neonatal hyperbilirubinemia. (4) In the hyperbilirubinemia group, the peak total serum bilirubin level of 211G>A homozygous neonates was higher than that of the wild-type neonates (p < 0.05). CONCLUSIONS: We noted that there was an association between neonates with unexplained indirect hyperbilirubinemia in Vietnam and the polymorphism of UGT1A1c.211G>A. In addition, the homozygous 211G>A polymorphism was related to the degree of hyperbilirubinemia. IMPACT: Our article provided data on UGT1A1 polymorphism distribution in the Vietnamese population, which have not been reported yet. Our findings revealed that mutations in UGT1A1 gene are risk factors for unexplained hyperbilirubinemia in Vietnamese neonates. Our article will strengthen the cognition of neonatal jaundice at the genetic level in the pediatric field in Vietnam.


Subject(s)
Glucuronosyltransferase/blood , Glucuronosyltransferase/genetics , Hyperbilirubinemia, Neonatal/blood , Hyperbilirubinemia, Neonatal/genetics , Polymorphism, Genetic , Promoter Regions, Genetic , Alleles , Bilirubin/blood , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Heterozygote , Homozygote , Humans , Infant, Newborn , Jaundice, Neonatal/blood , Jaundice, Neonatal/genetics , Male , Mutation , Polymerase Chain Reaction , Regression Analysis , Sequence Analysis, DNA , Vietnam
7.
Pediatr Res ; 78(5): 585-8, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26200705

ABSTRACT

BACKGROUND: Uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene mutation was shown to be responsible for neonatal hyperbilirubinemia. This study aimed to investigate whether UGT1A1 gene mutation is associated with neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations. METHODS: Two hundred and eighteen infants with hyperbilirubinemia (118 Heiyi Zhuang, 100 Han) and 190 control subjects (110 Heiyi Zhuang, 80 Han) were enrolled. Polymerase chain reaction and gene sequencing were used to detect the TATA-box and exon 1 of UGT1A1. RESULTS: (TA)7 insertion mutation, 211G>A (G71R), 686C>A (P229Q), and 189C>T (D63D) were detected. Logistic regression analysis showed odds ratios (OR) of 2.64 (95% confidence interval (CI) 1.64-4.24; P < 0.001) and 0.69 (95%CI 0.43-1.10; P = 0.115) for neonates who carried UGT1A1 G71R and (TA)7 insertion mutation, respectively. G71R homozygosity increased the odds of dangerous bilirubin levels by a factor 34.23, and G71R heterozygosity only by 2.10. CONCLUSION: We found that UGT1A1 G71R mutation is a risk factor for neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations. Meanwhile, the UGT1A1 (TA)7 insertion mutation is not associated with neonatal hyperbilirubinemia in the two ethnic groups.


Subject(s)
Asian People/genetics , Glucuronosyltransferase/genetics , Hyperbilirubinemia, Neonatal/genetics , Mutation , Bilirubin/blood , Biomarkers/blood , Case-Control Studies , Chi-Square Distribution , China , DNA Mutational Analysis/methods , Exons , Female , Genetic Association Studies , Genetic Markers , Genetic Predisposition to Disease , Heterozygote , Homozygote , Humans , Hyperbilirubinemia, Neonatal/blood , Hyperbilirubinemia, Neonatal/diagnosis , Hyperbilirubinemia, Neonatal/enzymology , Hyperbilirubinemia, Neonatal/ethnology , Infant, Newborn , Logistic Models , Male , Odds Ratio , Phenotype , Polymerase Chain Reaction , Risk Factors
8.
BMC Infect Dis ; 14: 390, 2014 Jul 14.
Article in English | MEDLINE | ID: mdl-25022748

ABSTRACT

BACKGROUND: Polymicrobial infections in adults and children are associated with increase in mortality, duration of intensive care and healthcare costs. Very few studies have characterized polymicrobial bloodstream infections in the neonatal unit. Considerable variation has been reported in incidence of polymicrobial infections and associated clinical outcomes. We characterized the risk factors and outcomes of polymicrobial bloodstream infections in our neonatal units in a tertiary hospital in North America. METHODS: In a retrospective case control study design, we identified infants in the neonatal intensive care unit with positive blood cultures at Texas Children's Hospital, over a 16-year period from January 1, 1997 to December 31, 2012. Clinical data from online databases were available from January 2009 to December 2012. For each polymicrobial bloodstream infection (case), we matched three infants with monomicrobial bloodstream infection (control) by gestational age and birth weight. RESULTS: We identified 2007 episodes of bloodstream infections during the 16 year study period and 280 (14%) of these were polymicrobial. Coagulase-negative Staphylococcus, Enterococcus, Klebsiella and Candida were the most common microbial genera isolated from polymicrobial infections. Polymicrobial bloodstream infections were associated with more than 3-fold increase in mortality and an increase in duration of infection. Surgical intervention was a significant risk factor for polymicrobial infection. CONCLUSION: The frequency and increased mortality emphasizes the clinical significance of polymicrobial bloodstream infections in the neonatal intensive care unit. Clinical awareness and focused research on neonatal polymicrobial infections is urgently needed.


Subject(s)
Bacteremia/diagnosis , Bacteremia/mortality , Coinfection/diagnosis , Coinfection/mortality , Intensive Care Units, Neonatal , Bacteremia/blood , Birth Weight , Candida , Case-Control Studies , Female , Humans , Incidence , Infant , Infant, Newborn , Klebsiella , Male , Retrospective Studies , Risk Factors , Staphylococcus , Texas , Treatment Outcome
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(11): 1183-7, 2014 Nov.
Article in Zh | MEDLINE | ID: mdl-25406570

ABSTRACT

Organic anion transporter 2 (OATP2) is an uptake transporter located on the basolateral membrane of human hepatocytes. It mediates the transportation of various organic solutes including bilirubin and impacts bilirubin metabolism. It is encoded by the gene of solute carrier organic anion transporter family member 1B1 and the gene variants that inhibit hepatic bilirubin uptake function may reduce the normal functional level of bilirubin elimination and result in neonatal hyperbilirubinemia. In recent years, some studies have indicated that variants of SLCO1B1 are associated with neonatal jaundice. This article reviews the research advance in SLCO1B1 with respect to the structure and function and the relationship between SLCO1B1 mutations and neonatal jaundice.


Subject(s)
Jaundice, Neonatal/genetics , Organic Anion Transporters/genetics , Glucosephosphate Dehydrogenase Deficiency/genetics , Humans , Infant, Newborn , Liver-Specific Organic Anion Transporter 1/genetics , Polymorphism, Genetic
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(5): 483-8, 2014 May.
Article in Zh | MEDLINE | ID: mdl-24856997

ABSTRACT

OBJECTIVE: To study the distribution of mutations of UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and its relationship with hyperbilirubinemia among neonates with hyperbilirubinemia of Guangxi Heiyi Zhuang nationality. METHODS: Total genomic DNA was extracted from the blood of 100 neonates with hyperbilirubinemia (case group) and 100 neonates without hyperbilirubinemia (control group), all of whom were selected from Guangxi Heiyi Zhuang population. TATA box and all exons of UGT1A1 gene were amplified by PCR and directly sequenced. RESULTS: (TA)7 insertion mutation in TATA box, G71R missense mutation in exon 1, and 4 single nucleotide polymorphisms (SNPs) (rs199539868, rs114982090, rs1042640 and rs8330) in exon 5 were observed. The allele frequency of G71R mutation in the case group was significantly higher than that in the control group (P<0.01). There were no significant differences in the genotype distribution and allele frequency of TATA box mutation and SNPs (rs1042640 and rs8330) between the two groups (P>0.05). The logistic regression analysis showed that the odds ratios (95% confidence intervals) of UGT1A1 TATA box mutation, G71R mutation, and SNPs (rs1042640 and rs8330) associated with the development of neonatal hyperbilirubinemia were 0.846 (0.440, 1.629), 3.932 (1.745, 8.858), 0.899 (0.364, 2.222), respectively. CONCLUSIONS: (TA)7 insertion mutation and G71R missense mutation of UGT1A1 gene are common mutation types in neonates with hyperbilirubinemia of Guangxi Heiyi Zhuang nationality. Four SNPs (rs199539868, rs114982090, rs1042640, and rs8330) was first reported in China. UGT1A1 G71R missense mutation is a risk factor for hyperbilirubinemia in neonates of Guangxi Heiyi Zhuang nationality.


Subject(s)
Glucuronosyltransferase/genetics , Hyperbilirubinemia, Neonatal/genetics , Mutation , China/ethnology , Humans , Infant, Newborn , Logistic Models , Polymorphism, Single Nucleotide , TATA Box
11.
ACS Appl Mater Interfaces ; 16(6): 6868-6878, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38294964

ABSTRACT

Osteosarcoma (OS) is considered the most frequent type of primary malignant bone tumor. Currently, radiotherapy, photodynamic (PDT), and other therapies for osteosarcoma are limited by tumor hypoxia and single efficacy and serve side-effects. Herein, we reported a microalgal drug delivery system (SpiD), doxorubicin (DOX)-loaded Spirulina platensis (Spi) for OS therapy. The specific surface of Spirulina platensis allowed for effective loading of DOX via surface channels and electrostatic interactions. Under 650 nm laser irradiation, SpiD enabled high oxygen production by photosynthesis and enhanced reactive oxygen species (ROS) generation via chlorophyll-assisted photosensitization, synergistically killing tumor cells with the released DOX. Combined chemotherapy and enhanced PDT mediated by SpiD exerted synergic antitumor effects and resulted in potent therapeutic efficacy in orthotopic osteosarcoma mice. Furthermore, SpiD could reduce the side-effects of chemotherapy, showing excellent blood and tissue safety. Taken together, this microalgal drug delivery system provided a natural, efficient, safe, and inexpensive strategy for OS treatment.


Subject(s)
Bone Neoplasms , Nanoparticles , Osteosarcoma , Photochemotherapy , Spirulina , Animals , Mice , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Osteosarcoma/drug therapy , Drug Delivery Systems , Bone Neoplasms/drug therapy , Cell Line, Tumor
12.
Adv Mater ; 36(24): e2312275, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38277492

ABSTRACT

Patients diagnosed with inflammatory bowel disease (IBD) exhibit a notable prevalence of psychiatric disorders, such as anxiety and depression. Nevertheless, the etiology of psychiatric disorders associated with IBD remains uncertain, and an efficacious treatment approach has yet to be established. Herein, an oral hydrogel strategy (SP@Rh-gel) is proposed for co-delivery of Spirulina platensis and rhein to treat IBD and IBD-associated anxiety and depression by modulating the microbiota-gut-brain axis. SP@Rh-gel improves the solubility, release characteristics and intestinal retention capacity of the drug, leading to a significant improvement in the oral therapeutic efficacy. Oral administration of SP@Rh-gel can reduce intestinal inflammation and rebalance the disrupted intestinal microbial community. Furthermore, SP@Rh-gel maintains intestinal barrier integrity and reduces the release of pro-inflammatory factors and their entry into the hippocampus through the blood-brain barrier, thereby inhibiting neuroinflammation and maintaining neuroplasticity. SP@Rh-gel significantly alleviates the colitis symptoms, as well as anxiety- and depression-like behaviors, in a chronic colitis mouse model. This study demonstrates the significant involvement of the microbiota-gut-brain axis in the development of IBD with psychiatric disorders and proposes a safe, simple, and highly efficient therapeutic approach for managing IBD and comorbid psychiatric disorders.


Subject(s)
Anxiety , Depression , Hydrogels , Inflammatory Bowel Diseases , Microalgae , Animals , Mice , Depression/drug therapy , Hydrogels/chemistry , Anxiety/drug therapy , Inflammatory Bowel Diseases/drug therapy , Microalgae/chemistry , Spirulina/chemistry , Gastrointestinal Microbiome/drug effects , Disease Models, Animal , Humans , Administration, Oral , Colitis/drug therapy
13.
ACS Nano ; 17(14): 14161-14175, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37406357

ABSTRACT

The oral form of insulin is more convenient and has better patient compliance than subcutaneous or intravenous insulin. Current oral insulin preparations, however, cannot overcome the enzyme barrier, chemical barrier, and epithelial barrier of the gastrointestinal tract completely. In this study, a microalgae-based oral insulin delivery strategy (CV@INS@ALG) was developed using Chlorella vulgaris (CV)-based insulin delivery system cross-linking with sodium alginate (ALG). CV@INS@ALG could overcome the gastrointestinal barrier, protect insulin from harsh gastric conditions, and achieve a pH-responsive drug release in the intestine. CV@INS@ALG might contribute to two mechanisms of insulin absorption, including direct insulin release from the delivery system and endocytosis by M cells and macrophages. In the streptozotocin (STZ)-induced type 1 diabetic mouse model, CV@INS@ALG showed a more effective and long-lasting hypoglycemic effect than direct insulin injection and did not cause any damage to the intestinal tract. Additionally, the long-term oral administration of the carrier CV@ALG effectively ameliorated gut microbiota disorder, and significantly increased the abundance of probiotic Akkermansia in db/db type 2 diabetic mice, thereby enhancing the insulin sensitivity of mice. Microalgal insulin delivery systems could be degraded and metabolized in the intestinal tract after oral administration, showing good biodegradability and biosafety. This insulin delivery strategy based on microalgal biomaterials provides a natural, efficient, and multifunctional solution for oral insulin delivery.


Subject(s)
Chlorella vulgaris , Diabetes Mellitus, Experimental , Microalgae , Humans , Mice , Animals , Insulin , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Hydrogels/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Drug Carriers/therapeutic use , Hydrogen-Ion Concentration , Administration, Oral , Drug Delivery Systems
14.
Nat Commun ; 14(1): 3069, 2023 05 27.
Article in English | MEDLINE | ID: mdl-37244895

ABSTRACT

Diagnostic and therapeutic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, we present a flexible, biodegradable photonic device called iCarP with a micrometer scale air gap between a refractive polyester patch and the embedded removable tapered optical fiber. ICarP combines the advantages of light diffraction by the tapered optical fiber, dual refractions in the air gap, and reflection inside the patch to obtain a bulb-like illumination, guiding light towards target tissue. We show that iCarP achieves large area, high intensity, wide spectrum, continuous or pulsatile, deeply penetrating illumination without puncturing the target tissues and demonstrate that it supports phototherapies with different photosensitizers. We find that the photonic device is compatible with thoracoscopy-based minimally invasive implantation onto beating hearts. These initial results show that iCarP could be a safe, precise and widely applicable device suitable for internal organs and tissue illumination and associated diagnosis and therapy.


Subject(s)
Optics and Photonics , Phototherapy , Optical Fibers , Photosensitizing Agents , Equipment Design
15.
Open Life Sci ; 17(1): 221-229, 2022.
Article in English | MEDLINE | ID: mdl-35415244

ABSTRACT

We aimed to investigate the effect of the genetic mutant G71R (c. 211G > A) in uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) on the glucuronidation of unconjugated bilirubin. The UGT1A1 wild-type and mutant G71R gene sequences were inserted into the lentiviral vector GV358 plasmid and then transfected into COS-7 cells. Real-time polymerase chain reaction and western blot analyses were used to determine mRNA and protein expression levels of UGT1A1, respectively. High-performance liquid chromatography was used to quantitate the levels of conjugated bilirubin. The results showed no significant difference in the mRNA and protein expression levels between the UGT1A1 wild-type and G71R homozygous and heterozygous mutants. The level of conjugated bilirubin reached a maximum in wild-type UGT1A1-transfected COS-7 cells. However, relative to the UGT1A1 wild-type, conjugated bilirubin concentrations were 71 and 22% with G71R heterozygous- and G71R homozygous-transfected COS-7 cells, respectively. In conclusion, we successfully established in vitro cell models of the UGT1A1 wild-type and the G71R homozygous and heterozygous mutants using a lentiviral vector. Furthermore, the catalytic activity for unconjugated bilirubin was lower in the mutant G71R than the UGT1A1 wild-type enzyme, and a weaker effect was observed in the homozygote.

16.
Nat Commun ; 13(1): 1413, 2022 03 17.
Article in English | MEDLINE | ID: mdl-35301299

ABSTRACT

Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Amifostine is a promising selective radioprotector for normal tissues. However, its oral application in intestinal radioprotection remains challenging. Herein, we use microalga Spirulina platensis as a microcarrier of Amifostine to construct an oral delivery system. The system shows comprehensive drug accumulation and effective radioprotection in the whole small intestine that is significantly superior to free drug and its enteric capsule, preventing the radiation-induced intestine injury and prolonging the survival without influencing the tumor regression. It also shows benefits on the gut microbiota homeostasis and long-term safety. Based on a readily available natural microcarrier, this work presents a convenient oral delivery system to achieve effective radioprotection for the whole small intestine, providing a competitive strategy with great clinical translation potential.


Subject(s)
Gastrointestinal Microbiome , Microalgae , Neoplasms , Radiation-Protective Agents , Homeostasis , Humans , Intestines , Neoplasms/drug therapy , Radiation-Protective Agents/pharmacology , Radiation-Protective Agents/therapeutic use
17.
Article in English | MEDLINE | ID: mdl-33073511

ABSTRACT

Surface-enhanced Raman scattering (SERS) technique has been regarded as one of the most important research methods in the field of single-molecule science. Since the previous decade, the application of nanoparticles for in vivo SERS imaging becomes the focus of research. To enhance the performance of SERS imaging, researchers have developed several SERS nanotags such as gold nanostars, copper-based nanomaterials, semiconducting quantum dots, and so on. The development of Raman equipment is also necessary owing to the current limitations. This review describes the recent advances of SERS nanoparticles and their applications for in vivo imaging in detail. Specific examples highlighting the in vivo cancer imaging and treatment application of SERS nanoparticles. A perspective on the challenges and opportunities of nanoparticles in SERS in vivo imaging is also provided. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.


Subject(s)
Diagnostic Imaging , Metal Nanoparticles , Nanostructures , Spectrum Analysis, Raman , Gold , Nanotechnology
18.
Theranostics ; 11(8): 3580-3594, 2021.
Article in English | MEDLINE | ID: mdl-33664849

ABSTRACT

Rationale: Hypoxia is one of the crucial restrictions in cancer radiotherapy (RT), which leads to the hypoxia-associated radioresistance of tumor cells and may result in the sharp decline in therapeutic efficacy. Methods: Herein, living photosynthetic microalgae (Chlorella vulgaris, C. vulgaris), were used as oxygenators, for in situ oxygen generation to relieve tumor hypoxia. We engineered the surface of C. vulgaris (CV) cells with calcium phosphate (CaP) shell by biomineralization, to form a biomimetic system (CV@CaP) for efficient tumor delivery and in-situ active photosynthetic oxygenation reaction in tumor. Results: After intravenous injection into tumor-bearing mice, CV@CaP could remarkably alleviate tumor hypoxia by continuous oxygen generation, thereby achieving enhanced radiotherapeutic effect. Furthermore, a cascade phototherapy could be fulfilled by the chlorophyll released from photosynthetic microalgae combined thermal effects under 650 nm laser irradiation. The feasibility of CV@CaP-mediated combinational treatment was finally validated in an orthotropic breast cancer mouse model, revealing its prominent anti-tumor and anti-metastasis efficacy in hypoxic-tumor management. More importantly, the engineered photosynthetic microalgae exhibited excellent fluorescence and photoacoustic imaging properties, allowing the self-monitoring of tumor therapy and tumor microenvironment. Conclusions: Our studies of this photosynthetic microsystem open up a new dimension for solving the radioresistance issue of hypoxic tumors.


Subject(s)
Chlorella vulgaris/metabolism , Mammary Neoplasms, Experimental/metabolism , Mammary Neoplasms, Experimental/therapy , Microalgae/metabolism , Tumor Hypoxia/physiology , Animals , Biomimetics/methods , Biomineralization , Calcium Phosphates/metabolism , Cell Line, Tumor , Combined Modality Therapy , Female , Mammary Neoplasms, Experimental/diagnostic imaging , Mice , Mice, Inbred BALB C , Oxygen/metabolism , Photoacoustic Techniques , Photosynthesis , Phototherapy/methods , Precision Medicine , Tumor Stem Cell Assay
19.
ACS Appl Bio Mater ; 4(5): 3729-3738, 2021 05 17.
Article in English | MEDLINE | ID: mdl-35006803

ABSTRACT

Because of the emergent evolution of multidrug-resistant (MDR) bacteria, resistance to traditional antibiotics has been increasingly causing public health concerns that it can rapidly overcome the development of antibacterial agents. Here, we demonstrated a facile electrodeposition method to prepare silver peroxysulfite (Ag7O8HSO4, AOHS) superpyramids on band-aids with extraordinary antibacterial performance. The porous structure and the sharp apex of AOHS superpyramids could facilitate the release of high-valence silver ions, which possess highly efficient MDR bacteria-killing effect and keep long-term antibacterial activity (>99% killing efficiency, recycle at least 4 times) because of their superior destruction capability of the membrane of the bacteria. A layer of copper was further evaporated onto the AOHS pyramids decorated on a band-aid, which could promote wound tissue angiogenesis and prohibit bacterial infection simultaneously, and finally accelerate the healing process in MDR bacteria-infected wound in vivo. The simple and low-cost fabrication process, as well as the outstanding antibacterial performance, make AOHS pyramids have promising applications in bacterial infection and practical sterilization fields, especially toward multidrug-resistant bacteria.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biocompatible Materials/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Wound Healing/drug effects , Amides/chemistry , Amides/pharmacology , Anti-Bacterial Agents/chemistry , Bacterial Infections/drug therapy , Biocompatible Materials/chemistry , Humans , Materials Testing , Microbial Sensitivity Tests , Particle Size , Silver/chemistry , Silver/pharmacology , Sulfites/chemistry , Sulfites/pharmacology
20.
Sci Adv ; 7(48): eabi9265, 2021 Nov 26.
Article in English | MEDLINE | ID: mdl-34818040

ABSTRACT

Design of innovative strategies for oral drug delivery is particularly promising for intestinal disease treatment. However, many obstacles such as poor therapeutic efficacy and low bioavailability and biocompatibility remain to be addressed. Here, we report a versatile formulation based on a helical-shaped cyanobacterium, Spirulina platensis (SP), loaded with curcumin (SP@Curcumin) for the treatment of colon cancer and colitis, two types of intestinal diseases. In radiotherapy for colon cancer, SP@Curcumin could mediate combined chemo- and radiotherapy to inhibit tumor progression while acting as a radioprotector to scavenge reactive oxygen species induced by the high dose of x-ray radiation in healthy tissues. SP@Curcumin could also reduce the production of proinflammatory cytokines and thereby exerted anti-inflammatory effects against colitis. The oral drug delivery system not only leveraged the biological properties of microalgal carriers to improve the bioavailability of loaded drugs but also performed excellent antitumor and anti-inflammation efficacy for intestinal disease treatment.

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