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Chemical Science Jul 2023Polymersomes are vesicular nanostructures enclosed by a bilayer-membrane self-assembled from amphiphilic block copolymers, which exhibit higher stability compared with... (Review)
Review
Polymersomes are vesicular nanostructures enclosed by a bilayer-membrane self-assembled from amphiphilic block copolymers, which exhibit higher stability compared with their biological analogues ( liposomes). Due to their versatility, polymersomes have found various applications in different research fields such as drug delivery, nanomedicine, biological nanoreactors, and artificial cells. However, polymersomes prepared with high molecular weight components typically display low permeability to molecules and ions. It hence remains a major challenge to balance the opposing features of robustness and permeability of polymersomes. In this review, we focus on the design and strategies for fabricating permeable polymersomes, including polymersomes with intrinsic permeability, the formation of nanopores in the membrane bilayers by protein insertion, and the construction of stimuli-responsive polymersomes. Then, we highlight the applications of permeable polymersomes in the fields of biomimetic nanoreactors, artificial cells and organelles, and nanomedicine, to underline the challenges in the development of polymersomes as soft matter with biomedical utilities.
PubMed: 37449076
DOI: 10.1039/d3sc01707a -
Frontiers in Cellular and Infection... 2023There are several clinical and molecular predictors of responses to antidepressant therapy. However, these markers are either too subjective or complex for clinical use....
BACKGROUND
There are several clinical and molecular predictors of responses to antidepressant therapy. However, these markers are either too subjective or complex for clinical use. The gut microbiota could provide an easily accessible set of biomarkers to predict therapeutic efficacy, but its value in predicting therapy responses to acupuncture in patients with depression is unknown. Here we analyzed the predictive value of the gut microbiota in patients with postpartum depressive disorder (PPD) treated with acupuncture.
METHODS
Seventy-nine PPD patients were enrolled: 55 were treated with acupuncture and 24 did not received any treatment. The 17-item Hamilton depression rating scale (HAMD-17) was used to assess patients at baseline and after eight weeks. Patients receiving acupuncture treatment were divided into an acupuncture-responsive group or non-responsive group according to HAMD-17 scores changes. Baseline fecal samples were obtained from the patients receiving acupuncture and were analyzed by high-throughput 16S ribosomal RNA sequencing to characterize the gut microbiome.
RESULTS
47.27% patients responded to acupuncture treatment and 12.5% patients with no treatment recovered after 8-week follow-up. There was no significant difference in α-diversity between responders and non-responders. The β-diversity of non-responders was significantly higher than responders. and spp. were significantly enriched in acupuncture responders, and these organisms had an area under the curve of 0.76 and 0.66 for predicting responder patients, respectively.
CONCLUSIONS
and are may be useful predictive biomarkers to predict PPD patients likely to respond to acupuncture. Larger studies and validation in independent cohorts are now needed to validate our findings.
Topics: Female; Humans; Treatment Outcome; Acupuncture Therapy; Microbiota; Depressive Disorder; Biomarkers; Postpartum Period
PubMed: 38053532
DOI: 10.3389/fcimb.2023.1228940 -
Chemical Science Jul 2023Stimuli-responsive polymers can switch specific physical properties in response to a change of the environmental conditions. This behavior offers unique advantages in...
Stimuli-responsive polymers can switch specific physical properties in response to a change of the environmental conditions. This behavior offers unique advantages in applications where adaptive materials are needed. To tune the properties of stimuli-responsive polymers, a detailed understanding of the relationship between the applied stimulus and changes in molecular structure as well as the relationship between the latter and macroscopic properties is required, which until now has required laborious methods. Here, we present a straightforward way to investigate the progressing trigger, the change of the chemical composition of the polymer and the macroscopic properties simultaneously. Thereby, the response behavior of the reversible polymer is studied with molecular sensitivity and spatial as well as temporal resolution utilizing Raman micro-spectroscopy. Combined with two-dimensional correlation analysis (2DCOS), this method reveals the stimuli-response on a molecular level and determines the sequence of changes and the diffusion rate inside the polymer. Due to the label-free and non-invasive approach, it is furthermore possible to combine this method with the investigation of macroscopic properties revealing the response of the polymer to the external stimulus on both the molecular and the macroscopic level.
PubMed: 37416726
DOI: 10.1039/d3sc01455j -
Chemical Society Reviews Aug 2023Chirality is a fundamental property which plays a major role in chemistry, physics, biological systems and materials science. Chiroptical artificial molecular motors... (Review)
Review
Chirality is a fundamental property which plays a major role in chemistry, physics, biological systems and materials science. Chiroptical artificial molecular motors (AMMs) are a class of molecules which can convert light energy input into mechanical work, and they hold great potential in the transformation from simple molecules to dynamic systems and responsive materials. Taking distinct advantages of the intrinsic chirality in these structures and the unique opportunity to modulate the chirality on demand, chiral AMMs have been designed for the development of light-responsive dynamic processes including switchable asymmetric catalysis, chiral self-assembly, stereoselective recognition, transmission of chirality, control of spin selectivity and biosystems as well as integration of unidirectional motion with specific mechanical functions. This review focuses on the recently developed strategies for chirality-led applications by the class of intrinsically chiral AMMs. Finally, some limitations in current design and challenges associated with recent systems are discussed and perspectives towards promising candidates for responsive and smart molecular systems and future applications are presented.
PubMed: 37581608
DOI: 10.1039/d3cs00247k -
MicroPublication Biology 2023CUTie2 is a FRET-based cGMP biosensor tested so far only in cells. To expand its use to multicellular organisms we generated two transgenic strains that express the...
CUTie2 is a FRET-based cGMP biosensor tested so far only in cells. To expand its use to multicellular organisms we generated two transgenic strains that express the biosensor in a tissue-dependent manner. CUTie2 expression and subcellular localization was verified by confocal microscopy. The performance of CUTie2 was analyzed on dissected larval brains by hyperspectral microscopy and flow cytometry. Both approaches confirmed its responsivity, and the latter showed a rapid and reversible change in the fluorescence of the FRET acceptor upon cGMP treatment. This validated reporter system may prove valuable for studying cGMP signaling at organismal level.
PubMed: 38094098
DOI: 10.17912/micropub.biology.000887 -
BioRxiv : the Preprint Server For... Dec 2023The melanocortin-3 receptor (MC3R) acts presynaptically to regulate GABA release from agouti-related protein (AgRP) nerve terminals and thus may be a negative regulator...
The melanocortin-3 receptor (MC3R) acts presynaptically to regulate GABA release from agouti-related protein (AgRP) nerve terminals and thus may be a negative regulator of multiple circuits involved in feeding behavior and energy homeostasis. Here, we examined the role of MC3R in regulating the response to various anorexigenic agents. Our findings reveal that genetic deletion or pharmacological inhibition of MC3R improves the dose responsiveness to Glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss. An enhanced anorectic response to other agents, including the acute satiety factors peptide YY (PYY) and cholecystokinin (CCK) and the long-term adipostatic factor, leptin, demonstrated that increased sensitivity to anorectic agents is a generalized result of MC3R antagonism. Enhanced neuronal activation in multiple nuclei, including ARH, VMH, and DMH, was observed using Fos immunohistochemistry following low-dose liraglutide in MC3R knockout mice (), supporting the hypothesis that the MC3R is a negative regulator of circuits regulating multiple aspects of feeding behavior. The enhanced anorectic response in mice after administration of GLP1 analogs was also independent of the incretin effects and malaise induced by GLP1R analogs, suggesting that MC3R antagonists may have value in enhancing the dose-response range of obesity therapeutics.
PubMed: 38106197
DOI: 10.1101/2023.12.05.570114 -
Bioactive Materials May 2024Peptide molecules have design flexibility, self-assembly ability, high biocompatibility, good biodegradability, and easy functionalization, which promote their... (Review)
Review
Peptide molecules have design flexibility, self-assembly ability, high biocompatibility, good biodegradability, and easy functionalization, which promote their applications as versatile biomaterials for tissue engineering and biomedicine. In addition, the functionalization of self-assembled peptide nanomaterials with other additive components enhances their stimuli-responsive functions, promoting function-specific applications that induced by both internal and external stimulations. In this review, we demonstrate recent advance in the peptide molecular design, self-assembly, functional tailoring, and biomedical applications of peptide-based nanomaterials. The strategies on the design and synthesis of single, dual, and multiple stimuli-responsive peptide-based nanomaterials with various dimensions are analyzed, and the functional regulation of peptide nanomaterials with active components such as metal/metal oxide, DNA/RNA, polysaccharides, photosensitizers, 2D materials, and others are discussed. In addition, the designed peptide-based nanomaterials with temperature-, pH-, ion-, light-, enzyme-, and ROS-responsive abilities for drug delivery, bioimaging, cancer therapy, gene therapy, antibacterial, as well as wound healing and dressing applications are presented and discussed. This comprehensive review provides detailed methodologies and advanced techniques on the synthesis of peptide nanomaterials from molecular biology, materials science, and nanotechnology, which will guide and inspire the molecular level design of peptides with specific and multiple functions for function-specific applications.
PubMed: 38327824
DOI: 10.1016/j.bioactmat.2024.01.023 -
Nanomaterials (Basel, Switzerland) Nov 2023Worldwide, hypoxia-related conditions, including cancer, COVID-19, and neuro-degenerative diseases, often lead to multi-organ failure and significant mortality. Oxygen,... (Review)
Review
Worldwide, hypoxia-related conditions, including cancer, COVID-19, and neuro-degenerative diseases, often lead to multi-organ failure and significant mortality. Oxygen, crucial for cellular function, becomes scarce as levels drop below 10 mmHg (<2% O), triggering mitochondrial dysregulation and activating hypoxia-induced factors (HiFs). Herein, oxygen nanobubbles (OnB), an versatile oxygen delivery platform, offer a novel approach to address hypoxia-related pathologies. This review explores OnB oxygen delivery strategies and systems, including diffusion, ultrasound, photodynamic, and pH-responsive nanobubbles. It delves into the nanoscale mechanisms of OnB, elucidating their role in mitochondrial metabolism (TFAM, PGC1alpha), hypoxic responses (HiF-1alpha), and their interplay in chronic pathologies including cancer and neurodegenerative disorders, amongst others. By understanding these dynamics and underlying mechanisms, this article aims to contribute to our accruing knowledge of OnB and the developing potential in ameliorating hypoxia- and metabolic stress-related conditions and fostering innovative therapies.
PubMed: 38063756
DOI: 10.3390/nano13233060 -
BioRxiv : the Preprint Server For... Aug 2023Breast tumors overexpressing human epidermal growth factor receptor (HER2) confer intrinsic resistance to endocrine therapy (ET), and patients with HER2/ estrogen...
BACKGROUND
Breast tumors overexpressing human epidermal growth factor receptor (HER2) confer intrinsic resistance to endocrine therapy (ET), and patients with HER2/ estrogen receptor-positive (HER2+/HR+) breast cancer (BCa) are less responsive to ET than HER2-/ER+. However, real-world evidence reveals that a large subset of HER2+/ER+ patients receive ET as monotherapy, positioning this treatment pattern as a clinical challenge. In the present study, we developed and characterized two distinct models of ET-resistant (ETR) HER2+/ER+ BCa to identify possible therapeutic vulnerabilities.
METHODS
To mimic ETR to aromatase inhibitors (AI), we developed two long-term estrogen-deprived (LTED) cell lines from BT-474 (BT474) and MDA-MB-361 (MM361). Growth assays, PAM50 molecular subtyping, genomic and transcriptomic analyses, followed by validation and functional studies, were used to identify targetable differences between ET-responsive parental and ETR-LTED HER2+/ER+ cells.
RESULTS
Compared to their parental cells, MM361 LTEDs grew faster, lost ER, and increased HER2 expression, whereas BT474 LTEDs grew slower and maintained ER and HER2 expression. Both LTED variants had reduced responsiveness to fulvestrant. Whole-genome sequencing of the more aggressive MM361 LTED model system identified exonic mutations in genes encoding transcription factors and chromatin modifiers. Single-cell RNA sequencing demonstrated a shift towards non-luminal phenotypes, and revealed metabolic remodeling of MM361 LTEDs, with upregulated lipid metabolism and antioxidant genes associated with ferroptosis, including . Combining the GPX4 inhibitor RSL3 with anti-HER2 agents induced significant cell death in both the MM361 and BT474 LTEDs.
CONCLUSIONS
The BT474 and MM361 AI-resistant models capture distinct phenotypes of HER2+/ER+ BCa and identify altered lipid metabolism and ferroptosis remodeling as vulnerabilities of this type of ETR BCa.
PubMed: 37662291
DOI: 10.1101/2023.08.21.554116 -
Nature Communications May 2024Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients...
Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.
Topics: Female; Humans; Ovarian Neoplasms; Deep Learning; Cystadenocarcinoma, Serous; Platinum; Middle Aged; Aged; Biomarkers, Tumor; Treatment Outcome; Neoplasm Grading; Cohort Studies; Adult; Reproducibility of Results
PubMed: 38762636
DOI: 10.1038/s41467-024-48667-6