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1.
Front Pharmacol ; 15: 1472662, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39444607

RESUMO

The majority of bispecific costimulatory antibodies in cancer immunotherapy are capable of exerting tumor-specific T-cell activation by simultaneously engaging both tumor-associated targets and costimulatory receptors expressed by T cells. The amount of trimeric complex formed when the bispecific antibody is bound simultaneously to the T cell receptor and the tumor-associated target follows a bell-shaped curve with increasing bispecific antibody exposure/dose. The shape of the curve is determined by the binding affinities of the bispecific antibody to its two targets and target expression. Here, using the case example of FAP-4-1BBL, a fibroblast activation protein alpha (FAP)-directed 4-1BB (CD137) costimulator, the impact of FAP-binding affinity on trimeric complex formation and pharmacology was explored using mathematical modeling and simulation. We quantified (1) the minimum number of target receptors per cell required to achieve pharmacological effect, (2) the expected coverage of the patient population for 19 different solid tumor indications, and (3) the range of pharmacologically active exposures as a function of FAP-binding affinity. A 10-fold increase in FAP-binding affinity (from a dissociation constant [KD] of 0.7 nM-0.07 nM) was predicted to reduce the number of FAP receptors needed to achieve 90% of the maximum pharmacological effect from 13,400 to 4,000. Also, the number of patients with colon cancer that would achieve 90% of the maximum effect would increase from 6% to 39%. In this work, a workflow to select binding affinities for bispecific antibodies that integrates preclinical in vitro data, mathematical modeling and simulation, and knowledge on target expression in the patient population, is provided. The early implementation of this approach can increase the probability of success with cancer immunotherapy in clinical development.

2.
Transl Oncol ; 50: 102151, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39388958

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a poor prognosis. Mono-immunotherapy, such as blockade of the PD-1/PD-L1 pathway, for PDAC has proven to be less effective. The systemic exertion of 4-1BB signaling enhanced antitumor immunity accompanied by hepatotoxicity, which is an obstacle for its clinical application. Our study exploits an oncolytic virus armed with 4-1BBL (VV-ΔTK-4L) to locally express 4-1BBL in the tumor microenvironment (TME), thus avoiding hepatotoxicity. VV-ΔTK-4L prolonged the survival time of a pancreatic tumor mouse model and modified the immune status of the TME and spleen. In the TME, the quantities of CD45+ cells, NK1.1+ cells, CD11c+ DCs, CD3+T, CD4+T, and CD8+T cells increased. Compared to VV-ΔTK treatment, VV-ΔTK-4L further increases the number of CD8+T cells with effector phenotypes, and downregulates exhaustion-related molecules on CD8+T cells, and does not increase the proportion of Foxp3+T cells. Thus, the TME of pancreatic cancer was converted from "cold" to "hot" by VV-ΔTK-4L. Blockade of the PD-1/PD-L1 pathway combined with VV-ΔTK-4L further significantly improves the survival ratio of a tumor-bearing mouse model. This study provides a systemic therapeutic strategy and approach for PDAC immunotherapy.

3.
J Funct Biomater ; 15(10)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39452591

RESUMO

Implant stability can be compromised by factors such as inadequate bone quality and infection, leading to potential implant failure. Ensuring implant stability and longevity is crucial for patient satisfaction and quality of life. In this multicenter, randomized, double-blind clinical trial, we assessed the impact of a bone bioactive liquid (BBL) on the Galaxy TS implant's performance, stability, and osseointegration. We evaluated the impact stability, osseointegration, and pain levels using initial stability quotient (ISQ) measurements, CBCT scans, and pain assessment post-surgery. Surface analysis was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). In vitro studies examined the BBL's effects on dental pulp pluripotent stem cells' (DPPSCs') osteogenesis and inflammation modulation in human macrophages. All implants successfully osseointegrated, as demonstrated by the results of our clinical and histological studies. The BBL-treated implants showed significantly lower pain scores by day 7 (p < 0.00001) and improved stability by day 30 (ISQ > 62.00 ± 0.59, p < 8 × 10-7). By day 60, CBCT scans revealed an increased bone area ratio in BBL-treated implants. AFM images demonstrated the BBL's softening and wettability effect on implant surfaces. Furthermore, the BBL promoted DPPSCs' osteogenesis and modulated inflammatory markers in human primary macrophages. This study presents compelling clinical and biological evidence that BBL treatment improves Galaxy TS implant stability, reduces pain, and enhances bone formation, possibly through surface tension modulation and immunomodulatory effects. This advancement holds promise for enhancing patient outcomes and implant longevity.

4.
Parasite Immunol ; 46(8-9): e13062, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39313933

RESUMO

The major histocompatibility complex (MHC) molecules play an integral role in the adaptive immune response to transmissible cancers through tumour antigen presentation and recognition of allogeneic MHC molecules. The transmissible devil facial tumours 1 and 2 (DFT1 and DFT2) modulate MHC-I antigen presentation to evade host immune responses and facilitate transmission of tumours cells to new Tasmanian devil (Sarcophilus harrisii) hosts. To enhance T-cell-driven tumour immunogenicity for vaccination and immunotherapy, DFT1 and DFT2 cells were co-transfected with (i) NLRC5 for MHC-I expression or CIITA for MHC-I and MHC-II expression, and (ii) a co-stimulatory molecule, either CD80, CD86 or 41BBL. The co-transfected DFT cells presented enhanced expression of MHC-I and/or MHC-II. As few devil-specific monoclonal antibodies exist, we used recombinant CTLA4 and 41BB fused to a fluorescent protein to confirm expression of cell surface CD80, CD86 and 41BBL. The capacity for these cells to induce T-cell responses including PD1 and IFNG expression was evaluated in in vitro co-culture assays with captive devil peripheral blood mononuclear cells (PBMCs). Although PBMC viability had increased, there was no evidence of enhanced T-cell activation. This system can be used to identify additional factors required to promote activation of naïve devil T-cells in vitro.


Assuntos
Antígeno B7-2 , Neoplasias Faciais , Marsupiais , Animais , Marsupiais/imunologia , Marsupiais/genética , Neoplasias Faciais/imunologia , Neoplasias Faciais/veterinária , Neoplasias Faciais/genética , Antígeno B7-2/metabolismo , Antígeno B7-2/genética , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Antígeno B7-1/imunologia , Linhagem Celular Tumoral , Linfócitos T/imunologia , Leucócitos Mononucleares/imunologia
5.
Aesthetic Plast Surg ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075324

RESUMO

BACKGROUND: Aesthetic enhancements to the buttock region have grown in demand due to media influence and evolving beauty standards. Using eye-tracking technology, we sought to uncover subconscious visual preferences regarding the buttock aesthetic. The objective of this investigation was to assess visual gaze patterns in assessing female buttocks among Caucasian and Asians through eye-tracking technology. MATERIALS AND METHODS: 67 participants viewed photographs of buttocks from various angles, and eye movements were analyzed using the Tobii Pro Nano eye-tracker. RESULTS: Males fixated on the intergluteal cleft for 0.96 ± 1.1 s and the thigh gap for 0.07 ± 0.2 s; while, females fixated for 0.81 ± 0.9 s and 0.06 ± 0.2 s on the same regions, respectively. Significant gender differences were observed in the intergluteal cleft (p = 0.002) and upper lateral buttock (p < 0.001). CONCLUSION: This study offers new insights into the observation of buttocks. The consistent attention toward the intergluteal cleft across demographics could be of potential significance in the aesthetic perception of buttocks. However, diverse gaze patterns also underscore the multifaceted nature of human attraction. These findings hold implications for plastic surgery, aesthetic medicine, and the sociocultural understanding of beauty. A deeper dive into aesthetic preferences is pivotal for a holistic understanding of human perceptions of attractive buttocks. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online instructions to Authors www.springer.com/00266 .

6.
Macromol Rapid Commun ; 45(14): e2400091, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38690992

RESUMO

Within bioplastics, natural poly(3-hydroxybutyrate) (PHB) stands out as fully biocompatible and biodegradable, even in marine environments; however, its high isotacticity and crystallinity limits its mechanical properties and hence its applications. PHB can also be synthesized with different tacticities via a catalytic ring-opening polymerization (ROP) of rac-ß-butyrolactone (BBL), paving the way to PHB with better thermomechanical and processability properties. In this work, the catalyst family is extended based on aluminum phenoxy-imine methyl catalyst [AlMeL2], that reveals efficient in the ROP of BBL, to the halogeno analogous complex [AlClL2]. As well, the impact on the ROP mechanism of different initiators is further explored with a particular focus in dimethylaminopyridine (DMAP), a hardly studied initiator for the ROP of BBL. A thorough mechanistic study is performed that evidences the presence of two concomitant DMAP-mediated mechanisms, that lead to either a DMAP or a crotonate end-capping group. Besides, in order to increase the possibilities of PHB post-polymerization functionalization, the introduction of a side-chain functionality is explored, establishing the copolymerization of BBL with ß-allyloxymethylene propiolactone (BPLOAll), resulting in well-defined P(BBL-co-BPLOAll) copolymers.


Assuntos
4-Butirolactona , Alumínio , Poli-Hidroxialcanoatos , Polimerização , Catálise , 4-Butirolactona/química , 4-Butirolactona/análogos & derivados , Poli-Hidroxialcanoatos/química , Alumínio/química , Estrutura Molecular , Hidroxibutiratos/química , Poli-Hidroxibutiratos
7.
Cell Rep ; 43(5): 114141, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38656869

RESUMO

The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for the therapeutic efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show that Batf3-lineage dendritic cells (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed that 4-1BBL is a major positive co-stimulatory signal provided by these DCs within the TME that translates to CD8+ T cell functional reinvigoration and tumor regression. Immunofluorescence and spatial transcriptomics on human tumor samples revealed clustering of Batf3+ DCs and CD8+ T cells, which correlates with anti-PD-1 efficacy. In addition, proximity to Batf3+ DCs within the TME is associated with CD8+ T cell transcriptional states linked to anti-PD-1 response. Our results demonstrate that Batf3+ DCs within the TME are critical for PD-1/PD-L1 blockade efficacy and indicate a major role for the 4-1BB/4-1BB ligand (4-1BBL) axis during this process.


Assuntos
Antígeno B7-H1 , Fatores de Transcrição de Zíper de Leucina Básica , Linfócitos T CD8-Positivos , Células Dendríticas , Receptor de Morte Celular Programada 1 , Proteínas Repressoras , Microambiente Tumoral , Animais , Humanos , Camundongos , Ligante 4-1BB/metabolismo , Ligante 4-1BB/genética , Antígeno B7-H1/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Células Dendríticas/imunologia , Inibidores de Checkpoint Imunológico/farmacologia , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Transdução de Sinais , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
8.
Vaccines (Basel) ; 12(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38543974

RESUMO

Natural 4-1BBL (CD137L) is a cell membrane-bound protein critical to the expansion, effector function, and survival of CD8+ T cells. We reported the generation of an active soluble oligomeric construct, SA-4-1BBL, with demonstrated immunoprevention and immunotherapeutic efficacy in various mouse tumor models. Herein, we developed an oncolytic adenovirus (OAd) for the delivery and expression of SA-4-1BBL (OAdSA-4-1BBL) into solid tumors for immunotherapy. SA-4-1BBL protein expressed by this construct produced T-cell proliferation in vitro. OAdSA-4-1BBL decreased cell viability in two mouse lung cancer cell lines, TC-1 and CMT64, but not in the non-cancerous lung MM14.Lu cell line. OAdSA-4-1BBL induced programmed cell death types I and II (apoptosis and autophagy, respectively), and autophagy-mediated adenosine triphosphate (ATP) release was also detected. Intratumoral injection of OAdSA-4-1BBL efficiently expressed the SA-4-1BBL protein in the tumors, resulting in significant tumor suppression in a syngeneic subcutaneous TC-1 mouse lung cancer model. Tumor suppression was associated with a higher frequency of dendritic cells and an increased infiltration of cytotoxic CD8+ T and NK cells into the tumors. Our data suggest that OAdSA-4-1BBL may present an efficacious alternative therapeutic strategy against lung cancer as a standalone construct or in combination with other immunotherapeutic modalities, such as immune checkpoint inhibitors.

9.
Sci Total Environ ; 913: 169660, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38159756

RESUMO

The flocculation dynamics within the bottom boundary layer (BBL) of tidal estuaries constitute a pivotal and intricate aspect entwined with hydrodynamics and morphodynamics. In microtidal estuaries, where saltwater intrusion occurs, the ensuing impacts on ecosystems, biological habitats, and human activities underscore necessity for comprehensive understanding. In pursuit of elucidating flocculation dynamics within estuarine BBLs, an extensive 25-hour survey was conducted throughout a complete tidal-cycle in the Huangmaohai estuary, China. This investigation encompassed the collection of data pertaining hydrodynamics, biochemical characteristics of suspended flocs within the BBL. The observed irregular semidiurnal tide was delineated into six distinct stages: I) Weak flood, II) Flood slack, III) Strong ebb, IV) Ebb slack, V) Strong flood and VI) Flood slack. The amalgamation of empirical findings and theoretical analyses has facilitated the development of conceptual model delineating the intricate processes and interactions of multiple factors within each stage (I-VI) in the BBL of a prototypical micro-tidal estuary. Notably, it reveals biological factors exhibit a significantly higher efficacy in estuarine flocculation dynamics within the BBL compared to the chemical ion attractions, attributable to variations in salinity. Further nuances emerged, indicating that semi-liquid extracellular polymeric substance (EPS) plays a substantial role in the formation of high-density flocs, particularly during periods of heightened turbulent shear conditions in flood and ebb times (I, III, V). Conversely, particulate biological debris predominantly contributes to low-density flocs characterized by a low settling velocity, particularly for large flocs >200 µm during tidal slacks (I, IV), and smaller median-sized flocs (70-200 µm) during flood or ebb times (III, V) due to turbulent induced breakage of bio-particles. This study underscores the significance of quantitative investigations into the biological components within individual flocs under estuarine hydrodynamics as a pivotal step towards comprehending flocculation mechanisms and predicting cohesive sediment transport within the BBLs of estuaries.

10.
Clin Plast Surg ; 50(4): 521-523, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37704319

RESUMO

Gluteal fat grafting is the fastest growing surgery in body contouring because of the powerful results that no other procedure can achieve. Efforts made to improve the safety of this procedure are reviewed.


Assuntos
Tecido Adiposo , Contorno Corporal , Humanos , Tecido Adiposo/transplante
11.
Clin Plast Surg ; 50(4): 587-601, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37704326

RESUMO

Low-cost, high-resolution ultrasound systems allow surgeons to visualize and manipulate the subcutaneous space and inject fat graft with millimeter accuracy.


Assuntos
Cirurgiões , Humanos , Ultrassonografia de Intervenção , Tecido Adiposo/diagnóstico por imagem
12.
Clin Plast Surg ; 50(4): 603-614, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37704327

RESUMO

Static injection, migration, and equalization allows for always subcutaneous-targeted fat grafting to either the deep or the superficial subcutaneous spaces.


Assuntos
Procedimentos de Cirurgia Plástica , Ultrassonografia de Intervenção , Humanos
13.
Cancer Immunol Immunother ; 72(11): 3567-3579, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37605009

RESUMO

Immunotherapy utilizing checkpoint inhibitors has shown remarkable success in the treatment of cancers. In addition to immune checkpoint inhibitors, immune co-stimulation has the potential to enhance immune activation and destabilize the immunosuppressive tumor microenvironment. CD137, also known as 4-1BB, is one of the potent immune costimulatory receptors that could be targeted for effective immune co-stimulation. The interaction of the 4-1BB receptor with its natural ligand (4-1BBL) generates a strong costimulatory signal for T cell proliferation and survival. 4-1BBL lacks costimulatory activity in soluble form. To obtain co-stimulatory activity in soluble form, a recombinant 4-1BBL protein was generated by fusing the extracellular domains of murine 4-1BBL to a modified version of streptavidin (SA-4-1BBL). Treatment with SA-4-1BBL inhibited the development of lung tumors in A/J mice induced by weekly injections of the tobacco carcinogen NNK for eight weeks. The inhibition was dependent on the presence of T cells and NK cells; depletion of these cells diminished the SA-4-1BBL antitumor protective effect. The number of lung tumor nodules was significantly reduced by the administration of SA-4-1BBL to mice during ongoing exposure to NNK. The data presented in this paper suggest that utilizing an immune checkpoint stimulator as a single agent generate a protective immune response against lung cancer in the presence of a carcinogen. More broadly, this study suggests that immune checkpoint stimulation can be extended to a number of other cancer types, including breast and prostate cancers, for which improved diagnostics can detect disease at the preneoplastic stage.


Assuntos
Neoplasias Pulmonares , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral , Camundongos , Animais , Carcinógenos/toxicidade , Linfócitos T , Ligante 4-1BB , Proteínas Recombinantes , Neoplasias Pulmonares/induzido quimicamente , Microambiente Tumoral
14.
J Transl Med ; 21(1): 506, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37501121

RESUMO

BACKGROUND: The activation of dendritic cells (DCs) is pivotal for generating antigen-specific T-cell responses to eradicate tumor cells. Hence, immunotherapies targeting this interplay are especially intriguing. Moreover, it is of interest to modulate the tumor microenvironment (TME), as this harsh milieu often impairs adaptive immune responses. Oncolytic viral therapy presents an opportunity to overcome the immunosuppression in tumors by destroying tumor cells and thereby releasing antigens and immunostimulatory factors. These effects can be further amplified by the introduction of transgenes expressed by the virus. METHODS: Lokon oncolytic adenoviruses (LOAd) belong to a platform of chimeric serotype Ad5/35 viruses that have their replication restricted to tumor cells, but the expression of transgenes is permitted in all infected cells. LOAd732 is a novel oncolytic adenovirus that expresses three essential immunostimulatory transgenes: trimerized membrane-bound CD40L, 4-1BBL and IL-2. Transgene expression was determined with flow cytometry and ELISA and the oncolytic function was evaluated with viability assays and xenograft models. The activation profiles of DCs were investigated in co-cultures with tumor cells or in an autologous antigen-specific T cell model by flow cytometry and multiplex proteomic analysis. Statistical differences were analyzed with Kruskal-Wallis test followed by Dunn's multiple comparison test. RESULTS: All three transgenes were expressed in infected melanoma cells and DCs and transgene expression did not impair the oncolytic activity in tumor cells. DCs were matured post LOAd732 infection and expressed a multitude of co-stimulatory molecules and pro-inflammatory cytokines crucial for T-cell responses. Furthermore, these DCs were capable of expanding and stimulating antigen-specific T cells in addition to natural killer (NK) cells. Strikingly, the addition of immunosuppressive cytokines TGF-ß1 and IL-10 did not affect the ability of LOAd732-matured DCs to expand antigen-specific T cells and these cells retained an enhanced activation profile. CONCLUSIONS: LOAd732 is a novel immunostimulatory gene therapy based on an oncolytic adenovirus that expresses three transgenes, which are essential for mediating an anti-tumor immune response by activating DCs and stimulating T and NK cells even under imunosuppressive conditions commonly present in the TME. These qualities make LOAd732 an appealing new immunotherapy approach.


Assuntos
Melanoma , Linfócitos T , Humanos , Proteômica , Melanoma/genética , Melanoma/terapia , Células Matadoras Naturais , Citocinas/metabolismo , Terapia Genética , Células Dendríticas , Microambiente Tumoral
15.
Microb Cell Fact ; 22(1): 67, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041591

RESUMO

BACKGROUND: Natural killer (NK) cell-based immunotherapies have demonstrated substantial potential for the treatment of hematologic malignancies. However, its application is limited due to the difficulty in the production of a large number of NK cells in vitro and the insufficient therapeutic efficacy against solid tumors in vivo. Engineered antibodies or fusion proteins targeting activating receptors and costimulatory molecules of NK cells have been developed to encounter these problems. They are mostly produced in mammalian cells with high cost and long processing times. Yeast systems, such as Komagataella phaffii, present a convenient manipulation of microbial systems with the key advantages of improved folding machinery and low cost. RESULTS: In this study, we designed an antibody fusion protein scFvCD16A-sc4-1BBL, composed of the single chain variant fragment (scFv) of anti-CD16A antibody and the three extracellular domains (ECDs) of human 4-1BBL in a single-chain format (sc) with the GS linker, aiming to boost NK cell proliferation and activation. This protein complex was produced in the K. phaffii X33 system and purified by affinity chromatography and size exclusion chromatography. The scFvCD16A-sc4-1BBL complex showed comparable binding abilities to its two targets human CD16A and 4-1BB as its two parental moieties (scFvCD16A and monomer ECD (mn)4-1BBL). scFvCD16A-sc4-1BBL specifically stimulated the expansion of peripheral blood mononuclear cell (PBMC)-derived NK cells in vitro. Furthermore, in the ovarian cancer xenograft mouse model, adoptive NK cell infusion combined with intraperitoneal (i.p) injection of scFvCD16A-sc4-1BBL further reduced the tumor burden and prolonged the survival time of mice. CONCLUSION: Our studies demonstrate the feasibility of the expression of the antibody fusion protein scFvCD16A-sc4-1BBL in K. phaffii with favourable properties. scFvCD16A-sc4-1BBL stimulates PBMC-derived NK cell expansion in vitro and improves the antitumor activity of adoptively transferred NK cells in a murine model of ovarian cancer and may serve as a synergistic drug for NK immunotherapy in future research and applications.


Assuntos
Leucócitos Mononucleares , Neoplasias Ovarianas , Feminino , Humanos , Animais , Camundongos , Ligantes , Ligante 4-1BB/uso terapêutico , Células Matadoras Naturais , Anticorpos , Neoplasias Ovarianas/tratamento farmacológico , Mamíferos
16.
J Exp Bot ; 74(14): 4169-4188, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37094831

RESUMO

WRKY transcription factors are involved in plant defense against pathogens. No WRKYs have been reported to be involved in resistance to tobacco brown spot disease caused by Alternaria alternata. Here, we found that NaWRKY3 plays a critical role in Nicotiana attenuata defense against A. alternata. NaWRKY3 bound and regulated many defense genes, including: lipoxygenase 3, ACC synthase 1, and ACC oxidase 1, three jasmonate- and ethylene-biosynthetic genes; feruloyl-CoA 6'-hydroxylase 1 (NaF6'H1), the biosynthetic gene for the phytoalexins scopoletin and scopolin; and three A. alternata resistance genes, the long non-coding RNA L2, NADPH oxidase (NaRboh D), and berberine bridge-like (NaBBL28). Silencing L2 reduced jasmonate concentrations and NaF6'H1 expression. NaRboh D-silenced plants were severely impaired in reactive oxygen species production and stomatal closure responses. NaBBL28 was the first A. alternata resistance BBL identified and was involved in the hydroxylation of 17-hydroxygeranyllinalool diterpene glycosides. NaWRKY3 bound to its own promoter but repressed its expression. Thus, we demonstrated that NaWRKY3 is a fine-tuned master regulator of the defense network against A. alternata in N. attenuata by regulating several signaling pathways and defense metabolites. This is the first time such an important WRKY has been identified in Nicotiana species, providing new insights into defense against A. alternata.


Assuntos
Ciclopentanos , Nicotiana , Nicotiana/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Glicosídeos
17.
J Cosmet Dermatol ; 22(5): 1536-1544, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36718828

RESUMO

OBJECTIVE: To investigate the efficacy and safety of broadband light (BBL) combined with intradermal injection of tranexamic acid for treating melasma. METHODS: 120 women with melasma admitted to our hospital from January 2021 to April 2022 were randomly categorized into the following groups: control group, treated with 250 mg tranexamic acid given orally twice daily, except during menstruation; group I, treated with BBL (Sciton, Inc., USA) monthly; group II, received intradermal injections of tranexamic acid monthly; and group III, treated with BBL with intradermal injection of tranexamic acid monthly. Treatment in each group lasted three months. The MASI (Melasma Area Severity Index) and VISIA (Canfield VISIA Complexion Analysis) were used for evaluation. RESULTS: After treatment course, MASI scores and VISIA brown spot and red zone ranking improved in all four groups (p < 0.05). The decrease in MASI scores and improvement rates of VISIA brown spot and red zone rankings were not significantly different among the control group, group I, and group II; however, the decreased MASI scores and improvement rates of VISIA brown spot and red zone rankings were significantly higher in group III than in the other three groups (p < 0.05). CONCLUSION: The effect of BBL combined with the intradermal injection of TA in the treatment of melasma is remarkable. This combination therapy can be an alternative and effective treatment for managing melasma.


Assuntos
Melanose , Ácido Tranexâmico , Feminino , Humanos , Terapia Combinada , Injeções Intradérmicas , Melanose/tratamento farmacológico , Resultado do Tratamento
18.
Aesthetic Plast Surg ; 47(5): 1896-1904, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36542093

RESUMO

OBJECTIVES: To describe characteristics of women with aesthetically ideal buttocks and differentiate them from women with normal buttocks. METHODS: Case-control study comparing anatomy of women with ideal buttocks (buttocks models) to women with normal buttocks using magnetic resonance images, anthropometric measurements and photography. RESULTS: Comparing to normal women, buttocks models have a narrower waist, narrower iliac crest, wider C point, wider hips and bigger and thicker gluteus maximus muscle (GMM). A bigger GMM adds more projection to the C point, point of maximum projection in the lateral view is 2.7 cm higher than the pubic bone. The amount of subcutaneous fat was equal in models and controls. CONCLUSIONS: Our study provides new knowledge regarding the tridimensional aspects of the beauty of the buttocks area. A beautiful buttock is a conjunction of adequate bony shape, muscle development, subcutaneous fat layer, and tight skin. Comparing to normal women, buttocks models have a narrower waist, narrower iliac crest, wider C point, wider hips and bigger and thicker Gluteus Maximus Muscle. Accurate understanding of the aesthetic goals in a given patient can guide surgical technique. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Imageamento por Ressonância Magnética , Humanos , Feminino , Nádegas/diagnóstico por imagem , Nádegas/cirurgia , Estudos de Casos e Controles , Antropometria , Estética
19.
Aesthetic Plast Surg ; 47(2): 666-681, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36214875

RESUMO

The most distinguished feature of the female silhouette is the buttock. As such, the Brazilian Butt Lift (BBL) has become the most popular plastic surgery procedures in recent years. Despite the popularity of this buttock reshaping and augmentation procedure, there remains no prevailing standard for evaluating, planning surgical design, and objectifying buttock size and shape outcomes. In fact, we have observed a wide range of preferred buttock size and shapes among our patients. We have previously published the BBL assessment tool that serves to guide patient communication of their preferred buttock size and shape. In this study, we demonstrate how the BBL assessment tool can serve to optimize Brazilian Buttock Lift results. We present 25 case studies of how the BBL assessment tool can serve to optimize BBL results by providing a guide for evaluation, surgical design, and objectification of outcomes.Level of Evidence IV Therapeutic study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .


Assuntos
Procedimentos de Cirurgia Plástica , Humanos , Feminino , Nádegas/cirurgia , Brasil , Estética
20.
Polymers (Basel) ; 14(23)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36501468

RESUMO

In this work, the electrospinning technique is used to fabricate a polymer-polymer coaxial structure nanofiber from the p-type regioregular polymer poly(3-hexylthiophene-2,5-diyl) (P3HT) and the n-type conjugated ladder polymer poly(benzimidazobenzophenanthroline) (BBL) of orthogonal solvents. Generally, the fabrication of polymeric coaxial nanostructures tends to be troublesome. Using the electrospinning technique, P3HT was successfully used as the core, and the BBL as the shell, thus conceptually forming a p-n junction that is cylindrical in form with diameters in a range from 280 nm to 2.8 µm. The UV-VIS of P3HT/PS blend solution showed no evidence of separation or precipitation, while the combined solutions of P3HT/PS and BBL were heterogeneous. TEM images show a well-formed coaxial structure that is normally not expected due to rapid reaction and solidification when mixed in vials in response to orthogonal solubility. For this reason, extruding it by using electrostatic forces promoted a quick elongation of the polymers while forming a concise interface. Single nanofiber electrical characterization demonstrated the conductivity of the coaxial surface of ~1.4 × 10-4 S/m. Furthermore, electrospinning has proven to be a viable method for the fabrication of pure semiconducting coaxial nanofibers that can lead to the desired fabrication of fiber-based electronic devices.

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