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1.
Immunology ; 172(3): 469-485, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38544333

ABSTRACT

Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis-promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T-cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis.


Subject(s)
CD8-Positive T-Lymphocytes , Endometriosis , STAT1 Transcription Factor , Stromal Cells , Endometriosis/immunology , Endometriosis/pathology , Endometriosis/metabolism , Female , CD8-Positive T-Lymphocytes/immunology , Humans , Animals , Mice , Stromal Cells/immunology , Stromal Cells/metabolism , STAT1 Transcription Factor/metabolism , Programmed Cell Death 1 Receptor/metabolism , Endometrium/immunology , Endometrium/pathology , Disease Models, Animal , Signal Transduction , Mice, Nude , Adult , CDC2 Protein Kinase/metabolism , Coculture Techniques , Cytokines/metabolism
2.
Int J Mol Sci ; 24(1)2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36614220

ABSTRACT

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.


Subject(s)
Penile Induration , Male , Humans , Penile Induration/drug therapy , Penis , Penile Erection , Injections , Stem Cells
3.
Am J Reprod Immunol ; 89(3): e13659, 2023 03.
Article in English | MEDLINE | ID: mdl-36412044

ABSTRACT

BACKGROUND: Endometriosis is a benign gynecological disease with the feature of estrogen dependence and inflammation. The function of autophagy and the correlation with inflammation were not yet revealed. METHODS: Autophagosomes were detected by transmission electron microscopy. Gene Expression Omnibus (GEO) database was referred to analyze the expression of autophagy-related genes. Quantification of mRNA and protein expression was examined by qRT-PCR and Western Blot. Immunohistochemistry was performed to explore the expression of proteins in tissues. The mouse model of endometriosis was performed to analyze the autophagic activity and effect of LXA4. RESULTS: The expression of autophagy-related genes in endometriotic lesions were unusually changed. The number of autophagosomes and LC3B-II expression was diminished, and p62 was increased in ectopic lesions from both patients and mice. Interleukin 1ß (IL1ß) attenuated the expression of LC3B and promoted the level p62. The autophagy activator MG-132 upregulated the expression of LC3B and reduced IL1ß, IL6, and p62. LXA4 reversed the inhibitory effect of IL1ß on the expression of LC3B and p62, and blocking the receptor of LXA4 AhR (aryl hydrocarbon receptor) resulted in the incapacitation of LXA4 to influence the effect of IL1ß. LXA4 depressed the phosphorylation of AKT and mTOR to against IL1ß, and blocking AhR negatively regulated the effect of LXA4 on AKT/mTOR pathway. LXA4 reduced the ectopic lesions and the expression of IL1ß and p62, but enhanced LC3B-II in endometriotic mouse models. CONCLUSION: In endometriosis, increased inflammation of ectopic lesions prominently depresses autophagy. LXA4 could regulate autophagy by suppressing inflammatory response through AhR/AKT/mTOR pathway.


Subject(s)
Endometriosis , Lipoxins , Humans , Female , Mice , Animals , Proto-Oncogene Proteins c-akt/metabolism , Endometriosis/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Endometrium/pathology , TOR Serine-Threonine Kinases/metabolism , Lipoxins/metabolism , Inflammation/metabolism , Autophagy
4.
Front Plant Sci ; 13: 967432, 2022.
Article in English | MEDLINE | ID: mdl-36110352

ABSTRACT

Mining novel and less utilized thousand grain weight (TGW) related genes are useful for improving wheat yield. In this study, a recombinant inbred line population from a cross between Zhongkemai 138 (ZKM138, high TGW) and Chuanmai 44 (CM44, low TGW) was used to construct a new Wheat 50K SNP array-derived genetic map that spanned 1,936.59 cM and contained 4, 139 markers. Based on this map, ninety-one quantitative trait loci (QTL) were detected for eight grain-related traits in six environments. Among 58 QTLs, whose superior alleles were contributed by ZKM138, QTgw.cib-6A was a noticeable major stable QTL and was also highlighted by bulked segregant analysis with RNA sequencing (BSR-Seq). It had a pyramiding effect on TGW enhancement but no significant trade-off effect on grain number per spike or tiller number, with two other QTLs (QTgw.cib-2A.2 and QTgw.cib-6D), possibly explaining the excellent grain performance of ZKM138. After comparison with known loci, QTgw.cib-6A was deduced to be a novel locus that differed from nearby TaGW2 and TaBT1. Seven simple sequence repeat (SSR) and thirty-nine kompetitive allele-specific PCR (KASP) markers were finally developed to narrow the candidate interval of QTgw.cib-6A to 4.1 Mb. Only six genes in this interval were regarded as the most likely candidate genes. QTgw.cib-6A was further validated in different genetic backgrounds and presented 88.6% transmissibility of the ZKM138-genotype and a 16.4% increase of TGW in ZKM138 derivatives. And the geographic pattern of this locus revealed that its superior allele is present in only 6.47% of 433 Chinese modern wheat varieties, indicating its potential contribution to further high-yield breeding.

5.
Andrology ; 10(6): 1143-1149, 2022 09.
Article in English | MEDLINE | ID: mdl-35701862

ABSTRACT

INTRODUCTION: Semen analysis (SA) plays a key role in guiding treatments of male reproductive diseases and infertility due to male factors; however, it remains challenging to conduct an accurate SA due to lack of standardization, highly subjective assessments, and problems with automated procedures. Therefore, quality assurance (QA) and teaching courses are essential for making the laboratory results more consistent. MATERIALS AND METHODS: The external quality assurance (EQA) scheme was organized by national human sperm bank technology training bases in Guangdong province in China between 2009 and 2020. Until 2020, 124 laboratories from China participated in the EQA program. The EQA scheme per year has been organized involving two semen aliquots for sperm concentration, two video recordings for motility, and two smears for sperm morphology. All samples used in the EQA scheme were obtained from different healthy donors or patients. RESULTS: We estimated that the median coefficient of variation (CV) of sperm concentration, ignoring the method used, was 26.6%. Using a 100 µm deep counting chamber led to a decreasing CV of 13.6%. For sperm motility, the median CV of nonprogressive motility was high (50.8%), but the CV of progressive motility (13.2%), immotile sperm (14.3%), and total motility (11.8%) were acceptable. The morphology assessment revealed large variability (44.4%) irrespective of the classification criteria. DISCUSSION: The reduction of interlaboratory variability is still a challenge during SA in China. Therefore, it is critical to increase awareness of joining EQA schemes and establish standardized training centers to follow WHO-recommended procedures toward Chinese standards.


Subject(s)
Semen , Sperm Motility , China , Humans , Male , Semen Analysis , Sperm Count , Spermatozoa
6.
Front Plant Sci ; 13: 1047899, 2022.
Article in English | MEDLINE | ID: mdl-36600920

ABSTRACT

Flag leaf size is a crucial trait influencing plant architecture and yield potential in wheat. A recombinant inbred line (RIL) population derived from the cross of W7268 and Chuanyu 12 was employed to identify quantitative trait loci (QTL) controlling flag leaf length (FLL), flag leaf width (FLW), and flag leaf area (FLA) in six environments and the best linear unbiased estimator (BLUE) datasets. Using a 55 K SNP-based genetic map, six major and stable QTL were detected with 6.33-53.12% of explained phenotypic variation. Except for QFlw.cib-4B.3, the other five major QTL were co-located within two intervals on chromosomes 2B and 2D, namely QFll/Fla.cib-2B and QFll/Flw/Fla.cib-2D, respectively. Their interactions and effects on the corresponding traits and yield-related traits were also assessed based on flanking markers. QFll/Fla.cib-2B showed pleiotropic effects on spikelet number per spike (SNS). QFlw.cib-4B.3 and QFll/Flw/Fla.cib-2D had effects on grain number per spike (GNS) and thousand-grain weight (TGW). Comparison analysis suggested that QFll/Fla.cib-2B was likely a new locus. Two candidate genes, TraesCS2B03G0222800 and TraesCS2B03G0230000, associated with leaf development within the interval of QFll/Fla.cib-2B were identified based on expression-pattern analysis, gene annotation, ortholog analysis, and sequence variation. The major QTL and markers reported here provide valuable information for understanding the genetic mechanism underlying flag leaf size as well as breeding utilization in wheat.

7.
Sci Rep ; 11(1): 15709, 2021 08 03.
Article in English | MEDLINE | ID: mdl-34344965

ABSTRACT

Calcaneal quantitative ultrasonography (QUS) is a useful prescreening tool for osteoporosis, while the dual-energy X-ray absorptiometry (DXA) is the mainstream in clinical practice. We evaluated the correlation between QUS and DXA in a Taiwanese population. A total of 772 patients were enrolled and demographic data were recorded with the QUS and DXA T-score over the hip and spine. The correlation coefficient of QUS with the DXA-hip was 0.171. For DXA-spine, it was 0.135 overall, 0.237 in females, and 0.255 in males. The logistic regression model using DXA-spine as a dependent variable was established, and the classification table showed 66.2% accuracy. A receiver operating characteristic (ROC) analyses with Youden's Index revealed the optimal cut-off point of QUS for predicting osteoporosis to be 2.72. This study showed a meaningful correlation between QUS and DXA in a Taiwanese population. Thus, it is important to pre-screen for osteoporosis with calcaneus QUS.


Subject(s)
Absorptiometry, Photon/methods , Bone Density , Calcaneus/diagnostic imaging , Osteoporosis/diagnostic imaging , Ultrasonography/methods , Aged , Aged, 80 and over , Female , Humans , Logistic Models , Male , Mass Screening , Middle Aged , Prognosis , ROC Curve , Sensitivity and Specificity , Taiwan
8.
Int Immunopharmacol ; 98: 107869, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34153673

ABSTRACT

OBJECTIVE: Spondyloarthritis (SpA) is mainly characterized by bone erosion, new bone formation, inflammation and potential disability. Epigallocatechin gallate (EGCG) has been proved to be closely related with the regulation of inflammation and bone metabolism. However, whether EGCG could improve SpA remains unclear. METHODS: SpA animal model was established using proteoglycan. Cell proliferation were measured by CCK-8 assay. The mRNA expression levels of genes were detected using qRT-PCR, protein levels were assessed via western blotting and immunohistochemistry. ELISA assay was performed to examined the inflammatory cytokine release. Lesions in spine cartilage tissues were observed using hematoxylin-eosin (HE) and Safranin O staining. Alkaline phosphatase (ALP) assay and Alizarin Red S staining was used to investigate osteoblast mineralization. RESULTS: We found that EGCG could inhibit inflammation and new bone formation in SpA mice. Besides, inflammatory factor expression and osteogenic differentiation in osteoblasts isolated from SpA mice were also decreased by EGCG. Further, EGCG treatment suppressed the activation of Wnt/ß-Catenin/COX-2 pathway and the activator of this pathway partially reversed the effects of EGCG on inflammation and osteoblast differentiation. CONCLUSIONS: EGCG repressed inflammatory responses and new bone formation, and further improved SpA through Wnt/ß-Catenin/COX-2 pathway. Our findings may provide a new thought for the prevention and treatment of SpA.


Subject(s)
Arthritis, Experimental/drug therapy , Catechin/analogs & derivatives , Osteogenesis/drug effects , Spondylarthritis/drug therapy , Wnt Signaling Pathway/drug effects , Administration, Oral , Animals , Arthritis, Experimental/immunology , Catechin/pharmacology , Catechin/therapeutic use , Cyclooxygenase 2/metabolism , Drug Evaluation, Preclinical , Humans , Male , Mice , Osteogenesis/immunology , Spondylarthritis/immunology , Wnt Signaling Pathway/immunology , beta Catenin/metabolism
9.
J Cancer Res Ther ; 16(4): 933-934, 2020.
Article in English | MEDLINE | ID: mdl-32930145

ABSTRACT

Hemothorax cannot always be treated by thoracic surgeon. Rapidly improved interventional pulmonology broadens the application of medical thoracoscopy. We attempt to share our experiences of medical thoracoscopy for hemothorax and discuss the value of medical thoracoscopy in pleural diseases. We reported a 76-year-old male with hemothorax who was cured by medical thoracoscopy under local anesthesia together with argon plasma coagulation. Moreover, final pathological diagnosis was acquired as pleural sarcomatoid carcinoma. The unusual manifestation under medical thoracoscopy of such a relative rare disease was also described in this paper. The medical thoracoscopy could be used successfully for hemothorax instead of treating with surgeon, especially for those who cannot tolerate procedure of operation or surgical thoracoscopy.


Subject(s)
Carcinosarcoma/pathology , Hemothorax/diagnosis , Hemothorax/therapy , Pleural Effusion/pathology , Thoracoscopy/methods , Aged , Biopsy , Carcinosarcoma/diagnosis , Carcinosarcoma/therapy , Hemothorax/pathology , Humans , Male , Pleural Diseases/diagnosis , Pleural Diseases/pathology , Pleural Diseases/therapy
10.
Exp Ther Med ; 20(3): 2099-2105, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32782522

ABSTRACT

The aim of the present study was to evaluate the effectiveness of interventional treatment of primary tracheal tumors through flexible bronchoscopy. The clinical data of 38 patients with primary tracheal tumours who underwent flexible bronchoscopy intervention therapy between January 2011 and January 2017 were retrospectively analyzed. The average time interval from onset of symptoms to the appearance of actual clinical manifestations in the 38 patients ranged from 0 to 60 months, with an average of 8.1±11.6 months and a median of 4.2 months. The rate of misdiagnosis at the first visit was 36.8% (14/38). After interventional treatment, the overall efficiency (complete + partial response) of airway stenosis recanalization in the 38 patients was 89.5%. In 3 patients with benign tumors, the anhelation score was reduced following treatment (1.00±0.77 vs. 3.13±1.21 at the pre-treatment stage; P<0.001). The overall survival rates of the 35 patients at 1, 3 and 5 years were 69.3, 48.7 and 20.3%, respectively. Therefore, flexible bronchoscopic intervention may effectively smoothen the airways of patients and relieve the symptoms of anhelation. Combining radiotherapy and chemotherapy may improve patient prognosis and safety.

11.
Am J Reprod Immunol ; 83(3): e13213, 2020 03.
Article in English | MEDLINE | ID: mdl-31802565

ABSTRACT

PROBLEM: The application of primary eutopic endometrial cells from endometriosis patients in research is restricted for short life span, dedifferentiation of hormone responsiveness. METHOD OF STUDY: Human telomerase reverse transcriptase (hTERT)-induced immortalized cells (iheESCs) were infected by lentivirus. mRNA level was examined by qRT-PCR, and protein expression was quantified by Western blot. CCK-8 and EdU assay were assigned to assess the proliferation. The migration and invasion of cells were assessed by transwell assay. Clone formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities. RESULTS: hTERT mRNA and protein were significantly expressed higher in iheESCs compared to primary cells. iheESCs grew without morphological change for 42 passages which is much longer than 18 passages of primary cells. There was no obvious difference between primary cells and iheESCs in growth, mobility, and chromosome karyotype. Furthermore, the expression of epithelial-mesenchymal transition (EMT) markers and estrogen/progesterone receptors remained unchanged. The decidualization of iheESCs could be induced by progesterone and cAMP. Estrogen increased the proliferation and mobility of iheESCs, and lipopolysaccharides (LPS) induced the IL-1ß and IL-6 promoting inflammatory response. The colony-forming ability of iheESCs, like primary cells, was lower than Ishikawa cells. In addition, tumorigenicity assay indicated that iheESCs were unable to trigger tumor formation in BALB/c nude mouse. CONCLUSIONS: This study established and characterized iheESCs that kept the cellular physiology of primary cells and were not available with tumorigenic ability. Thus, iheESCs would be useful as in vitro cell model to investigate pathogenesis of endometriosis.


Subject(s)
Endometriosis/pathology , Endometrium/cytology , Stromal Cells/cytology , Animals , Carcinogenesis , Cell Line, Transformed , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Female , Humans , Mice , Mice, Nude , Telomerase/metabolism , Tumor Stem Cell Assay
12.
ACS Appl Mater Interfaces ; 11(34): 30575-30584, 2019 Aug 28.
Article in English | MEDLINE | ID: mdl-31382742

ABSTRACT

A hypertensive emergency causes severe cardiovascular diseases accompanied by acute target organ damage, requiring rapid and smooth blood pressure (BP) reduction. Current medicines for treating hypertensive emergencies, such as sodium nitroprusside (SNP), require careful dose control to avoid side effects (e.g., cyanide poisoning). The clinical administration of SNP using intravenous injection or drip further restrict its usage for first aid or self-aid in emergencies. Here, we developed an antihypertensive microneedle (aH-MN) technique to transdermally deliver SNP in combination with sodium thiosulfate (ST) as a cyanide antidote in a painless way. Dissolvable microneedles loaded with SNP and ST were fabricated via the centrifugation casting method, where the SNPs were stably packaged in microneedles and would be immediately released into the systemic circulation via subcutaneous capillaries when aH-MNs penetrated the skin. The antihypertensive effects were demonstrated on spontaneously hypertensive rat models. Rapid and potent BP reduction was achieved via aH-MN treatment, fulfilling clinical BP-control requirements for hypertensive emergencies. The side effects including skin irritation and target organ damage of aH-MN therapies were evaluated; the combinative delivery of ST effectively suppressed these side effects induced by the consecutive intake of SNP. This study introduces an efficient and patient-friendly antihypertensive therapy with a favorable side-effect profile, particularly a controllable and self-administrable approach to treat hypertensive emergencies.


Subject(s)
Antihypertensive Agents , Hypertension/drug therapy , Needles , Skin/metabolism , Administration, Cutaneous , Animals , Antihypertensive Agents/chemistry , Antihypertensive Agents/pharmacology , Humans , Hypertension/metabolism , Hypertension/pathology , Rats
13.
Chem Commun (Camb) ; 55(69): 10222-10225, 2019 Aug 22.
Article in English | MEDLINE | ID: mdl-31360986

ABSTRACT

We report the formation and degradation of a unique guanidine cyclic diimide (GCDI) structure and GCDI-based polymers. The GCDI structure is readily formed under mild conditions. The X-ray crystal structure showed that the delocalized π-orbitals in the guanidine plane are significantly disrupted in the GCDI structure. Unlike amine-based imides, the GCDI structure readily degrades into the initial guanidine in protic solvents at ambient temperatures. Furthermore, poly(GCDI)s, a new category of polymers with the GCDI backbones, can be synthesized from guanidines and dianhydrides. Similar to the monomeric GCDIs, poly(GCDI)s are degraded in protic solvents unlike polyimides with high chemical stability.

14.
Org Lett ; 21(15): 5862-5866, 2019 Aug 02.
Article in English | MEDLINE | ID: mdl-31310138

ABSTRACT

A new method for 3-formalytion of indoles has been developed through electrochemical decarboxylation of glyoxylic acid with the amine as a dual function organocatalyst. The amine facilitated both the electrochemical decarboxylation and the nucleophilic reaction efficiently, whose loading can be as low as 1 mol %. This protocol has a broad range of functional group tolerance under ambient conditions. The gram-scale experiment has shown great potential in the synthetic application of this strategy.

15.
BMC Pulm Med ; 19(1): 125, 2019 Jul 10.
Article in English | MEDLINE | ID: mdl-31291926

ABSTRACT

BACKGROUND: Medical thoracoscopy is considered an overall safe procedure, whereas numbers of studies focus on complications of diagnostic thoracoscopy and talc poudrage pleurodesis. We conduct this study to evaluate the safety of medical thoracoscopy in the management of pleural diseases and to compare complications in different therapeutic thoracoscopic procedures. METHODS: A retrospective study was performed in 1926 patients, 662 of whom underwent medical thoracoscopy for diagnosis and 1264 of whom for therapeutic interventions of pleural diseases. Data on complications were obtained from the patients, notes on computer system, laboratory and radiographic findings. Chi-square test was performed to compare categorical variables and Fisher's exact test was used for small samples. RESULTS: The mean age was 51 ± 8.4 (range 21-86) years and 1117 (58%) were males. Diagnostic procedure was taken in 662 (34.4%) patients, whereas therapeutic procedure was taken in 1264 (65.6%) patients. Malignant histology was reported in 860 (44.6%) and 986 (51.2%) revealed benign pleural diseases. Eighty patients (4.2%) were not definitely diagnosed and they were considered as unidentified pleural effusion. One patient died during the creation of artificial pneumothorax, and the causes of death were supposed as air embolism or an inhibition of phrenic motoneurons and circulatory system. Complication of lung laceration was found in six patients (0.3%) and reexpansion pulmonary edema was observed in two patients (0.1%). Higher incidence of prolonged air leak was observed in bulla electrocoagulation group, in comparison with pleurodesis group. Moreover, pain and fever were the most frequently complications in pleurodesis group and cutaneous infection in entry site was the most frequently reported complication in pleural decortication of empyema group. CONCLUSIONS: Medical thoracoscopy is generally a safe and effective method, not only in the diagnosis of undiagnosed pleural effusions, but also in the management of pleural diseases. Mastering medical thoracoscopy well, improving patient management after the procedure and attempts to reduce the occurrence of post-procedural complications are the targets that physicians are supposed to achieve in the future.


Subject(s)
Pleural Effusion, Malignant/diagnosis , Pleural Effusion/diagnosis , Pleural Effusion/therapy , Pleurodesis , Thoracoscopy , Adult , Aged , Aged, 80 and over , Biopsy , Chi-Square Distribution , Exudates and Transudates , Female , Humans , Male , Middle Aged , Patient Safety , Pleura/pathology , Pleurodesis/adverse effects , Recurrence , Retrospective Studies , Talc/administration & dosage , Thoracoscopy/adverse effects , Tuberculosis/complications , Tuberculosis/diagnosis , Young Adult
16.
ACS Cent Sci ; 5(6): 960-969, 2019 Jun 26.
Article in English | MEDLINE | ID: mdl-31263755

ABSTRACT

The intracellular delivery of biomolecules is of significant importance yet challenging. In addition to the conventional delivery of nanomaterials that rely on biochemical pathways, vertical nanowires have been recently proposed to physically penetrate the cell membrane, thus enabling the direct release of biomolecules into the cytoplasm circumventing endosomal routes. However, due to the inherent attachment of the nanowires to a planar 2D substrate, nanowire cell penetrations are restricted to in vitro applications, and they are incapable of providing solution-based delivery. To overcome this structural limitation, we created polyethylenimine-functionalized microparticles covered with nanospikes, namely, "spiky particles", to deliver biomolecules by utilizing the nanospikes to penetrate the cell membrane. The nanospikes might penetrate the cell membrane during particle engulfment, and this enables the bound biomolecules to be released directly into the cytosol. TiO2 spiky particles were fabricated through hydrothermal routes, and they were demonstrated to be biocompatible with HeLa cells, macrophage-like RAW cells, and fibroblast-like 3T3-L1 cells. The polyethylenimine-functionalized spiky particles provided direct delivery of fluorescent siRNA into cell cytosol and functional siRNA for gene knockdown as well as successful DNA plasmid transfection which were difficult to achieve by using microparticles without nanospikes. The spiky particles presented a unique direct cell membrane penetrant vehicle to introduce biomolecules into cell cytosol, where the biomolecules might bypass conventional endocytic degradation routes.

17.
Org Lett ; 21(7): 1958-1962, 2019 04 05.
Article in English | MEDLINE | ID: mdl-30869908

ABSTRACT

Thiocyanate compounds are key intermediates in the synthesis of pharmaceuticals and other sulfur-containing organic compounds. Herein, we first report an electrochemical protocol to synthesize vinyl thiocyanates from decarboxylative coupling of cinnamic acids with NH4SCN in aqueous solution. This method provides thiocyanation products with broad functional group tolerance under ambient conditions.

18.
ACS Appl Mater Interfaces ; 11(5): 4809-4819, 2019 Feb 06.
Article in English | MEDLINE | ID: mdl-30628778

ABSTRACT

Real-time transdermal biosensing provides a direct route to quantify biomarkers or physiological signals of local tissues. Although microneedles (MNs) present a mini-invasive transdermal technique, integration of MNs with advanced nanostructures to enhance sensing functionalities has rarely been achieved. This is largely due to the fact that nanostructures present on MNs surface could be easily destructed due to friction during skin insertion. In this work, we reported a dissolvable polymer-coating technique to protect nanostructures-integrated MNs from mechanical destruction during MNs insertion. After penetration into the skin, the polymer could readily dissolve by interstitial fluids so that the superficial nanostructures on MNs could be re-exposed for sensing purpose. To demonstrate this technique, metallic and resin MNs decorated with vertical ZnO nanowires (vNWs) were employed as an example. Dissolvable poly(vinyl pyrrolidone) was spray-coated on the vNW-MNs surface as a protective layer, which effectively protected the superficial ZnO NWs when MNs penetrated the skin. Transdermal biosensing of H2O2 biomarker in skin tissue using the polymer-protecting MNs sensor was demonstrated both ex vivo and in vivo. The results indicated that polymer coating successfully preserved the sensing functionalities of the MNs sensor after inserting into the skin, whereas the sensitivity of the MN sensor without a coating protection was significantly compromised by 3-folds. This work provided unique opportunities of protecting functional nanomodulus on MNs surface for minimally invasive transdermal biosensing.


Subject(s)
Biosensing Techniques/instrumentation , Microinjections/instrumentation , Nanowires/chemistry , Needles , Animals , Equipment Design , Mice , Mice, Inbred C57BL , Models, Biological , Povidone/chemistry , Skin/chemistry , Swine , Zinc Oxide/chemistry
19.
ACS Appl Mater Interfaces ; 10(39): 33060-33069, 2018 Oct 03.
Article in English | MEDLINE | ID: mdl-30204401

ABSTRACT

Cisplatin is the first-line chemotherapeutic agent, but its systemic toxicity and side effects severely limit its clinical use. We report a microneedle technique to mediate the transdermal delivery of lipid-coated cisplatin nanoparticles (LCC-NPs) for efficient and safe cancer therapy. Cisplatin was encapsulated by tumor-targeting pH-responsive lipid nanoparticles with a high loading rate of 80%, and the encapsulation substantially increased the solubility of cisplatin and enhanced its antitumor efficiency in vitro. The LCC-NPs were embedded in dissolvable microneedles, and released from the microneedles after inserting into the skin. This enabled the nanoparticles to pass the stratum corneum for safe local delivery. An in vivo study with a xenograft tumor animal model demonstrated that microneedle arrays loaded with cisplatin nanoparticles significantly increased cytotoxicity and apoptosis in cancer cells with an apoptotic index of 58.6%, resulting in significantly reduced tumor volume and weight. Moreover, serum platinum, pulmonary toxicity, hepatotoxicity, and nephrotoxicity were not detected in vivo, indicating that this technique is biosafe. The cisplatin-nanoparticle microneedle system developed in this study may offer promising opportunities in cancer therapy for enhancing antitumor effects and reducing systemic toxicity and side effects.


Subject(s)
Cisplatin/administration & dosage , Nanoparticles/chemistry , Animals , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cisplatin/therapeutic use , Female , Head and Neck Neoplasms/drug therapy , Humans , In Situ Nick-End Labeling , Lipids/chemistry , Mice , Mice, Nude , Nanoparticles/administration & dosage
20.
Sci Rep ; 8(1): 12600, 2018 08 22.
Article in English | MEDLINE | ID: mdl-30135437

ABSTRACT

Many fields of applications require dispersion of hydrophobic particles in water, which is traditionally achieved by using surfactants or amphiphilic molecules to modify particle surfaces. However, surfactants or amphiphilic molecules may disturb the native solution or particles' surface hydrophobicity, limiting extended applications such as oil emulsion cleaning. Recently one example of 2 µm-size polystyrene microparticles covered with ZnO nanospikes has been shown to exhibit excellent dispersity in water in spite of surface hydrophobicity. Whether this anomalous dispersion phenomenon was applicable to other hydrophobic microparticle systems was still unclear and its application scope was limited. Here the anomalous dispersities of different hydrophobic spiky micro-objects were systematically explored. The results show that the anomalous dispersion phenomenon was universally observed on different hydrophobic spiky micro-objects including different hydrophobic coating, particle sizes, material compositions and core particle morphologies. In addition, the spiky micro-objects displayed anomalous dispersity in water without compromising surface hydrophobicity, and their applications for oil spills absorption and oil emulsion cleaning were demonstrated. This work offers unique insight on the nanospikes-mediated anomalous dispersion phenomenon of hydrophobic micro-object and potentially extends its applicability and application scopes.

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