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1.
Nano Lett ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012311

RESUMO

At near-parallel orientation, twisted bilayers of transition metal dichalcogenides exhibit interlayer charge transfer-driven out-of-plane ferroelectricity. Here, we report detailed electrical transport in a dual-gated graphene field-effect transistor placed on a 2.1° twisted bilayer WSe2. We observe hysteretic transfer characteristics and an emergent charge inhomogeneity with multiple local Dirac points evolving with an increasing electric displacement field (D). Concomitantly, we also observe a strong nonlocal voltage signal at D ∼ 0 V/nm that decreases rapidly with increasing D. A linear scaling of the nonlocal signal with longitudinal resistance suggests edge mode transport, which we attribute to the breaking of valley symmetry of graphene due to the spatially fluctuating electric field from the underlying polarized moiré domains. A quantitative analysis suggests the emergence of finite-size domains in graphene that modulate the charge and the valley currents simultaneously. This work underlines the impact of interfacial ferroelectricity that can trigger a new generation of devices.

2.
Bull Entomol Res ; 114(1): 134-148, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38178797

RESUMO

Aulacophora lewisii Baly (Coleoptera: Chrysomelidae) is an important pest of Luffa acutangula (L.) Roxb. (Cucurbitaceae) in India. Larvae of A. lewisii feed on the roots, while adults consume leaves of L. acutangula. In the current study, effects of three L. acutangula cultivars (Abhiskar, Debsundari, and Jaipur Long) on the life table parameters by age-stage, two-sex approach, and key digestive enzymatic activities (amylolytic, proteolytic, and lipolytic) of the larvae and adults of A. lewisii were determined. Further, nutrients (total carbohydrates, proteins, lipids, amino acids, and nitrogen content) and antinutrients (total phenols, flavonols, and tannins) present in the roots and leaves of three cultivars were estimated. The development time (egg to adult emergence) was fastest and slowest on Jaipur Long (31.80 days) and Abhiskar (40.91 days), respectively. Fecundity was highest and lowest on Jaipur Long (279.91 eggs) and Abhiskar (137.18 eggs), respectively. The intrinsic rate of increase (r) was lowest on Abhiskar (0.0511 day-1) and highest on Jaipur Long (0.0872 day-1). The net reproductive rate (R0) was lowest on Abhiskar (23.32 offspring female-1). The mean generation time (T) was shortest on Jaipur Long (52.59 days) and longest on Abhiskar (61.58 days). The amylolytic, proteolytic, and lipolytic activities of larvae and adults of A. lewisii were highest and lowest on Jaipur Long and Abhiskar, respectively. The lower level of nutrients and higher level of antinutrients influenced higher larval development time and lower fecundity of A. lewisii on Abhiskar than other cultivars. Our results suggest that Abhiskar cultivar could be promoted for cultivation.


Assuntos
Besouros , Cucurbitaceae , Luffa , Feminino , Animais , Besouros/fisiologia , Tábuas de Vida , Larva , Fenômenos Fisiológicos do Sistema Digestório
3.
Cytokine ; 156: 155913, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35640418

RESUMO

Cytokine therapies have shown promising results against cancers. Cytokines are secreted naturally from different bodily cells. These have fewer side effects but higher specificity than chemotherapy and radiation therapy. In leukemia, changes in normal hematopoiesis and defective leukocyte production limit the efficacy of immunotherapy by reducing the count of functional immune cells. Therefore, the treatment of leukemia needs advanced therapeutics that can target multiple cancer sustaining mechanisms. In combination therapy, using two different therapeutic agents affect cancer growth in many ways and sometimes gives synergistic effects. Here, we examined the effect of the ethanolic olive leaf extract (EOLE) and IL-28B in combination. N-N' Ethyl-nitrosourea (ENU) induced leukemia in Swiss albino mice was treated with EOLE for four weeks and IL-28B for one week after confirming the development of leukemia. The combination of EOLE and IL-28B significantly reduced the blast cell and total WBC counts in the peripheral blood, altered the levels of various cytokines in plasma, and induced the functional activity of NK cells in leukemic mice. The induced NK activity correlates with increased expression of perforin and granzyme studied at the gene level through real-time (RT)-PCR. The treatment of leukemic mice with combined EOLE and IL-28B has also caused an increased serum IL-10 and IFN-γ level, and reduced serum TGF-ß indicates improved overall immunity. Altogether, the combination of EOLE and IL-28B has given substantial therapeutic activity against leukemia.


Assuntos
Leucemia , Olea , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Etilnitrosoureia , Imunoterapia , Interferon gama/metabolismo , Leucemia/tratamento farmacológico , Camundongos , Olea/metabolismo , Extratos Vegetais/farmacologia
4.
J Chem Ecol ; 48(11-12): 802-816, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36333551

RESUMO

This study investigated effects of volatile blends released from undamaged (UD), insect-damaged [ID, plants fed by larvae of Spilosoma obliqua Walker (Lepidoptera: Arctiidae)] and mechanically-damaged (MD) plants of three green gram cultivars [PDM 54, Pusa Baisakhi and Samrat] including synthetic blends on the behavior of conspecific adult moths in Y-tube olfactometer bioassays. Females showed attraction towards volatile blends of UD, ID and MD plants of these green gram cultivars against the control solvent (CH2Cl2). The components of volatile blends in UD plants of three green gram cultivars are not similar, but no any difference was found among three cultivars in term of the attractive effect on the insect moths when volatile blends from UD plants of these three cultivars were tested against one another. Females were more attracted towards volatile blends of ID plants of a particular cultivar compared to UD plants of the same cultivar. Total amount of volatiles was higher in ID plants than UD plants. Some herbivore-induced plant volatiles - (Z)-3-hexenal, 1-hexanol, (Z)-3-hexenyl acetate, 2-octanol and ocimene were attractive to the insect moths. Females were attracted towards three synthetic blends resembling amounts present in natural volatile blends of ID plants of these three cultivars in Y-tube olfactometer and wind tunnel bioassays, suggesting that involvement of host-specific chemical cues in long-range host location by S. obliqua females. If attraction of adult S. obliqua to these synthetic volatile blends is upheld by field trials then these blends may find practical application in detection and monitoring of S. obliqua populations.


Assuntos
Mariposas , Compostos Orgânicos Voláteis , Animais , Feminino , Larva , Herbivoria , Plantas , Compostos Orgânicos Voláteis/farmacologia
5.
Nanotechnology ; 32(45)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34298522

RESUMO

Van der Waals (vdW) heterostructure is a type of metamaterial where multiple layers of 2D materials are vertically aligned at controlled misorientation. The relative rotation in between the adjacent layers, or the twist angle between them plays a crucial role in changing the electronic band structure of the superlattice. The assembly of multi-layers of precisely twisted two dimensional layered materials requires knowledge of the atomic structure at the edge of the flake. It may be artificially created by the 'tear and stack' process. Otherwise, the crystallographic orientation needs to be determined through invasive processes such as transmission electron microscopy or scanning tunneling microscopy, and via second-harmonic generation (SHG). Here, we demonstrate a simple and elegant transfer protocol using only an optical microscope as a edge identifier tool through which, controlled transfer of twisted homobilayer and heterobilayer transition metal dichalcogenides is performed with close to 100% yield. The fabricated twisted vdW heterostructures have been characterized by SHG, Raman spectroscopy and photoluminiscence spectroscopy, confirming the desired twist angle within ∼0.5° accuracy. The presented method is reliable, quick and prevents the use of invasive tools which is desirable for reproducible device functionalities.

6.
J Biochem Mol Toxicol ; 35(2): e22643, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32996240

RESUMO

Reactive oxygen species (ROS) are generated as by-product of cellular respiration and also due to the exposure of various xenobiotics, whereas mitochondrial electron transport chain is considered as the main source of ROS generation. The sequential addition to molecular oxygen gives rise to various forms of ROS like superoxide anion, peroxide, hydroxyl radical, hydroxyl ion, and so forth. However, the uncontrolled level of ROS generation and accumulation alters the body homeostasis. Excessive generation of ROS leads to oxidative stress and various kinds of diseases including cancer. To counteract ROS, enzymatic and nonenzymatic antioxidants' armory is available in our body. Apart from endogenous antioxidants, we are also consuming various exogenous antioxidants. Antioxidants protect us from ROS-mediated damages and inhibit ROS-induced carcinogenesis. Recent studies have revealed that antioxidants could also act as tumor-promoting agents. Various anticancer drugs are used to kill the cancer cells through the generation of oxidative stress in them, but the cancer cells can counteract the effect with the help of various endogenous as well as exogenous antioxidants. Our review will summarize the multifaceted relationship between antioxidants and carcinogenesis, and it will help to create new directions in antioxidant-based chemotherapy.


Assuntos
Antioxidantes/farmacologia , Carcinogênese/efeitos dos fármacos , Anticarcinógenos/farmacologia , Humanos , Neoplasias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
7.
J Chem Ecol ; 47(7): 664-679, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34196857

RESUMO

Larval Diaphania indica (Saunders) (Lepidoptera: Crambidae) cause complete defoliation of Trichosanthes anguina L. and reduce crop yield in India. Females lay eggs on the leaf surface, and therefore leaf surface waxes are potentially involved in host selection. Alkanes and free fatty acids are the major constituents of leaf surface waxes, so a study was conducted to determine whether these wax constituents from three T. anguina cultivars (MNSR-1, Baruipur Long, and Polo No.1) could act as short-range attractants and oviposition stimulants in D. indica females. Twenty n-alkanes from n-C14 to n-C36 and 13 free fatty acids from C12:0 to C21:0 were detected in the leaf surface waxes of these cultivars. Heptadecane and stearic acid were predominant among n-alkanes and free fatty acids, respectively, in these cultivars. Females showed attraction towards one leaf equivalent surface wax of each of these cultivars against solvent controls (petroleum ether) in Y-tube olfactometer bioassays. A synthetic blend of heptadecane, eicosane, hexacosane, and stearic acid, a synthetic blend of hexacosane and stearic acid, and a synthetic blend of pentadecane and stearic acid comparable to amounts present in one leaf equivalent surface wax of MNSR-1, Baruipur Long, and Polo No.1, respectively, were short-range attractants and oviposition stimulants in D. indica. Female egg laying responses were similar to each of these blends, providing information that could be used to developing baited traps in integrated pest management (IPM) programs.


Assuntos
Cucurbitaceae/metabolismo , Mariposas/fisiologia , Oviposição/efeitos dos fármacos , Ceras/farmacologia , Alcanos/análise , Alcanos/isolamento & purificação , Alcanos/farmacologia , Animais , Análise Discriminante , Ácidos Graxos não Esterificados/análise , Ácidos Graxos não Esterificados/isolamento & purificação , Ácidos Graxos não Esterificados/farmacologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Larva/efeitos dos fármacos , Larva/fisiologia , Mariposas/crescimento & desenvolvimento , Olfatometria , Folhas de Planta/metabolismo , Ceras/química , Ceras/isolamento & purificação
8.
Nutr Cancer ; 72(7): 1200-1210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31591915

RESUMO

Aim: Pineapple (Ananas comosus (L.) Merr.) is a good source of bromelain (B) and also contain peroxidase. The objective of this study is isoaltion of bromelain plus peroxidase (BP) from the pineapple fruit to evaluate the anticancer activity of BP from the pineapple fruit of Tripura, compared to commercial bromelain against ascitic Dalton's lymphoma cells (DLA) in mice. Methods: By acetone precipitation BP was isolated from the pineapple. Animals bearing DLA, receive B and BP orally for 15 alternative days. Apoptotic proteins are assayed using western blot. Results: BP treated mice showed recover of hemoglobin and WBC count compared to control lymphoma animal. The animal showed significant reduction of body weight due to reduced tunor load and elevated reactive oxygen species (ROS) production, elevated levels of vitamin C and vitamin E and other antioxidants in blood after BP treatment. Histology of liver and kidney also shows restored architecture in BP treated animal compared to only B treated group. BP treatment upregulates the cytochrome C, BAD, and BAX protein and downregulates the Bcl-2 and NF-kß occuring upon BP treatment in the DLA cells collected from lymphoma animal. This induce the apoptosis of DLA cells in lymphoma animal and reduce the tumor load. Conclusion: The present findings suggest that BP from pineapple improves the survival of the induced lymphoma animal compared to only B which may be used as therapeutic target.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Bromelaínas/farmacologia , Linfoma não Hodgkin/tratamento farmacológico , Peroxidase/farmacologia , Extratos Vegetais/farmacologia , Ananas/química , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Linhagem Celular Tumoral , Humanos , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Regulação para Cima/efeitos dos fármacos
9.
Bull Entomol Res ; 110(6): 756-766, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32484147

RESUMO

Diaphania indica (Saunders) (Lepidoptera: Crambidae) is an important phytophagous pest of Trichosanthes anguina L. in India. We studied life table parameters by age-stage, two-sex, amylolytic and proteolytic activities, and food utilization parameters of D. indica on the leaves of three T. anguina cultivars (Baruipur Long, Polo No. 1 and MNSR-1). Further, nutrients (total carbohydrates, proteins, lipids, amino acids and nitrogen) and antinutrients (total phenols, flavonols and tannins) in leaves were determined. The development time (egg to adult emergence) was the shortest on MNSR-1 (19.79 d) and the longest on Polo No. 1 (25.72 d). Fecundity was the highest and lowest on MNSR-1 (259 eggs) and Polo No. 1 (151.22 eggs), respectively. The lowest intrinsic rate of increase (rm) and net reproductive rate (R0) of D. indica on Polo No. 1 were 0.1112 d-1 and 27.22 offspring individual-1, respectively. The mean generation time (T) was the shortest on MNSR-1 (23.99 days) and the longest on Polo No. 1 (29.70 d). The larvae of D. indica fed with MNSR-1 had the highest level of amylolytic and proteolytic activities, and the lowest activities were in the larvae fed with Polo No. 1. The fifth-instar larvae fed with Polo No. 1 had the lowest consumption index and growth rate. The higher larval development time and lower fecundity of D. indica on Polo No. 1 were due to the lower level of nutrients and a higher level of antinutrients than other cultivars. Our results concluded that Polo No. 1 cultivar could be suggested for cultivation.


Assuntos
Mariposas/crescimento & desenvolvimento , Mariposas/fisiologia , Trichosanthes/química , Fenômenos Fisiológicos da Nutrição Animal , Animais , Fenômenos Fisiológicos do Sistema Digestório , Feminino , Fertilidade , Larva/crescimento & desenvolvimento , Larva/fisiologia , Tábuas de Vida , Masculino , Trichosanthes/classificação
10.
Bull Entomol Res ; 110(2): 231-241, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31559934

RESUMO

Aphis craccivora Koch (Hemiptera: Aphididae) is an important pest of Lathyrus sativus L. plants, and causes retarded plant growth and loss of seed production. The insect sucks cell sap from flowers and lays nymphs on flowers. Hence, an attempt has been made to observe whether flower surface wax compounds (alkanes and free fatty acids) from two cultivars (BIO L 212 Ratan and Nirmal B-1) of L. sativus could act as short-range attractant and stimulant for nymph laying by adult viviparous females. The n-hexane extracts of flower surface waxes were analyzed by TLC, GC-MS and GC-FID analyses. Twenty one and 22 n-alkanes between n-C12 and n-C36 were detected in BIO L 212 Ratan and Nirmal B-1, respectively; whereas 12 free fatty acids between C12:0 and C22:0 were identified in both cultivars. Pentadecane and tridecanoic acid were predominant n-alkane and free fatty acid, respectively. One flower equivalent surface wax of both cultivars served as short-range attractant and stimulant for nymph laying through Y-tube choice experiments and I-tube viviparity assays, respectively, by adult viviparous females. A synthetic blend of nonacosane, tridecanoic acid and linoleic acid, and a synthetic blend of tetradecane, pentadecane, nonacosane, tridecanoic acid and linoleic acid resembling in amounts as present in one flower equivalent surface wax of BIO L 212 Ratan and Nirmal B-1, respectively, served as short-range attractant and stimulant for nymph laying by adult viviparous females. This study suggests that both these blends could be used in lures in the development of baited traps in pest management programmes.


Assuntos
Afídeos/fisiologia , Flores/química , Lathyrus/química , Viviparidade não Mamífera , Ceras/química , Animais , Comportamento de Escolha , Feminino , Ninfa , Olfatometria
11.
Antimicrob Agents Chemother ; 60(4): 2257-64, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26833163

RESUMO

Population level variation of drug metabolism phenotype (DMP) has great implications in treatment outcome, drug-related side effects, and resistance development. In this study, we used a gas chromatography-time of flight-mass spectrometry (GC-TOF-MS)-based untargeted urine metabolomics approach to understand the DMP of a tuberculosis (TB) patient cohort (n= 20) from Tripura, a state in the northeastern part of India. Urine samples collected at different postdose time points (2 h, 6 h, 12 h, 24 h, 36 h, and 48 h) from these newly diagnosed TB patients receiving first-line anti-TB drugs were analyzed, and we have successfully detected three of the four first-line drugs,viz, isoniazid (INH), ethambutol (ETB), and pyrazinamide (PZA). The majority of their known metabolites, acetyl-isoniazid (AcINH), isonicotinic acid (INA), isonicotinuric acid (INTA), 2,2'-(ethylenediimino)-dibutyric acid (EDBA), 5-hydroxypyrazinamide (5OH-PZA), pyrazinoic acid (POA), and 5-hydroxypyrazinoic acid (5OH-POA), were also detected. Analyzing the variation in abundances of drugs and their known metabolites and calculating the metabolic ratios in these samples, we offer comprehensive DMP information on this small patient cohort that represents Tripura, India. The majority (75%) of these patients are found to be slow acetylators of INH. The average metabolic ratios of POA/PZA and 5OH-POA/POA are 3.16 ± 3.03 and 6.09 ± 6.15, respectively. Employing correlation analysis of the metabolomics metadata and a manual prediction of drug catabolism, we have proposed 2-aminobutyric acid (AABA) as a novel metabolite of ETB. These observations indicate the usefulness of GC-MS-based metabolomics to characterize the DMP at a population level and also to identify novel drug metabolites.


Assuntos
Aminobutiratos/urina , Antituberculosos/urina , Etambutol/urina , Metabolômica , Tuberculose Pulmonar/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Biotransformação , Estudos de Casos e Controles , Cromatografia Gasosa , Etambutol/uso terapêutico , Feminino , Humanos , Índia , Isoniazida/uso terapêutico , Isoniazida/urina , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/fisiologia , Pirazinamida/uso terapêutico , Pirazinamida/urina , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
12.
iScience ; 27(4): 109366, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38510127

RESUMO

Triple-negative breast cancer (TNBC) contributes greatly to mortality of breast cancer, demanding new targetable options. We have shown that TNBC patients have high ΔNp63 expression in tumors. However, the function of ΔNp63 in established TNBC is yet to be explored. In current studies, targeting ΔNp63 with inducible CRISPR knockout and Histone deacetylase inhibitor Quisinostat showed that ΔNp63 is important for tumor progression and metastasis in established tumors by promoting myeloid-derived suppressor cell (MDSC) survival through tumor necrosis factor alpha. Decreasing ΔNp63 levels are associated with decreased CD4+ and FOXP3+ T-cells but increased CD8+ T-cells. RNA sequencing analysis indicates that loss of ΔNp63 alters multiple MDSC properties such as lipid metabolism, chemotaxis, migration, and neutrophil degranulation besides survival. We further demonstrated that targeting ΔNp63 sensitizes chemotherapy. Overall, we showed that ΔNp63 reprograms the MDSC-mediated immunosuppressive functions in TNBC, highlighting the benefit of targeting ΔNp63 in chemotherapy-resistant TNBC.

13.
Pest Manag Sci ; 79(11): 4295-4308, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37357178

RESUMO

BACKGROUND: First to third instars of Diaphania indica (Saunders) (Lepidoptera: Crambidae) feed on the lower surface of leaves, while fourth and fifth instars gregariously consume leaves of Trichosanthes anguina L. After defoliating, the caterpillar also attacks flowers and fruits of the plant and finally, results in loss of crop yield. Therefore, behavioral responses of D. indica adults were investigated to volatiles from undamaged (UD), insect-damaged (ID, plants after feeding by D. indica larvae) and jasmonic acid (JA) treated T. anguina plants. RESULTS: Females showed attraction to volatiles of UD and ID plants of three T. anguina cultivars [MNSR-1 (MNS), Baruipur Long (BAR) and Polo No. 1 (POLO)] in Y-tube olfactometer bioassays. Females did not show significant negative responses from volatiles of JA treated plants. Females were more attracted to volatiles of ID plants than UD plants. Females showed attraction to volatiles of UD or ID plants compared to JA treated plants. Females were attracted to certain synthetic blends resembling volatiles of insect-damaged MNS, BAR and POLO plants in olfactometer bioassays. Females could not distinguish among these three certain synthetic blends in olfactometer bioassays. A synthetic blend of 3Z-hexen-1-ol, α-pinene, hexyl acetate, benzyl alcohol and 6Z-nonenal at mole ratios of 1.47:1.20:1:1.82:1.21 was prepared at 20 mg/mL dichloromethane and 100 µL when used as lure in funnel traps resulted in the capture of the highest number of D. indica adults in field trails. CONCLUSION: The earlier five-component chemical lure could be used in traps in an integrated pest management program of the insect pest, D. indica. © 2023 Society of Chemical Industry.

14.
Mol Oral Microbiol ; 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37902166

RESUMO

Fibroblasts are ubiquitous mesenchymal cells that exhibit considerable molecular and functional heterogeneity. Besides maintaining stromal integrity, oral fibroblast subsets are thought to play an important role in host-microbe interaction during injury repair, which is not well explored in vivo. Here, we characterize a subset of fibroblast lineage labeled by paired-related homeobox-1 promoter activity (Prx1Cre+ ) in oral mucosa and skin and demonstrate these fibroblasts readily respond to microbial products to facilitate the normal wound healing process. Using a reporter mouse model, we determined that Prx1Cre+ fibroblasts had significantly higher expression of toll-like receptors 2 and 4 compared to other fibroblast populations. In addition, Prx1 immunopositive cells exhibited heightened activation of inflammatory transcription factor NF-κB during the early wound healing process. At the cytokine level, CXCL1 and CCL2 were significantly upregulated by Prx1Cre+ fibroblasts at baseline and upon LPS stimulation. Importantly, lineage-specific knockout to prevent NF-κB activation in Prx1Cre+ fibroblasts drastically impaired both oral and skin wound healing processes, which was linked to reduced macrophage infiltration, failure to resolve inflammation, and clearance of bacteria. Together, our data implicate a pro-healing role of Prx1-lineage fibroblasts by facilitating early macrophage recruitment and bacterial clearance.

15.
J Exp Med ; 220(3)2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36584405

RESUMO

Injuries that heal by fibrosis can compromise organ function and increase patient morbidity. The oral mucosal barrier has a high regenerative capacity with minimal scarring, but the cellular mechanisms remain elusive. Here, we identify distinct postnatal paired-related homeobox-1+ (Prx1+) cells as a critical fibroblast subpopulation that expedites mucosal healing by facilitating early immune response. Using transplantation and genetic ablation model in mice, we show that oral mucosa enriched with Prx1+ cells heals faster than those that lack Prx1+ cells. Lineage tracing and scRNA-seq reveal that Prx1+ fibroblasts exhibit progenitor signatures in physiologic and injured conditions. Mechanistically, Prx1+ progenitors accelerate wound healing by differentiating into immunomodulatory SCA1+ fibroblasts, which prime macrophage recruitment through CCL2 as a key part of pro-wound healing response. Furthermore, human Prx1+ fibroblasts share similar gene and spatial profiles compared to their murine counterpart. Thus, our data suggest that Prx1+ fibroblasts may provide a valuable source in regenerative procedures for the treatment of corneal wounds and enteropathic fibrosis.


Assuntos
Cicatriz , Cicatrização , Camundongos , Animais , Humanos , Cicatrização/fisiologia , Fibrose , Fibroblastos/fisiologia , Imunomodulação
16.
Sci Transl Med ; 15(686): eabl4414, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36888695

RESUMO

Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and are generally considered to be antitumorigenic. Using single-cell RNA sequencing and functional analysis of multiple triple-negative breast cancer (TNBC) and basal tumor samples, we observed a unique subcluster of Socs3highCD11b-CD27- immature NK cells that were present only in TNBC samples. These tumor-infiltrating NK cells expressed a reduced cytotoxic granzyme signature and, in mice, were responsible for activating cancer stem cells through Wnt signaling. NK cell-mediated activation of these cancer stem cells subsequently enhanced tumor progression in mice, whereas depletion of NK cells or Wnt ligand secretion from NK cells by LGK-974 decreased tumor progression. In addition, NK cell depletion or inhibition of their function improved anti-programmed cell death ligand 1 (PD-L1) antibody or chemotherapy response in mice with TNBC. Furthermore, tumor samples from patients with TNBC and non-TNBC revealed that increased numbers of CD56bright NK cells were present in TNBC tumors and were correlated to poor overall survival in patients with TNBC. Together, our findings identify a population of protumorigenic NK cells that may be exploited for both diagnostic and therapeutic strategies to improve outcomes for patients with TNBC.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Células Matadoras Naturais , Antígeno B7-H1/metabolismo , Microambiente Tumoral
17.
Chem Biol Interact ; 354: 109807, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-34999049

RESUMO

AIM: Our previous work depicted that benzo(a)pyrene (BaP)-induced lung cancer associated pulmonary redox imbalance and inflammation were effectively regulated by the combinatorial treatment of IL-27 and IL-28B. So in continuation of that finding the present study was designed to reveal the inflammation regulating signaling network modulated by IL-27 and IL-28B treatment related to BaP-induced lung cancer. METHODS: Male Swiss albino mice were treated with BaP to induce lung tumor. Then they received individual as well as combinatorial treatment of IL-27 and IL-28B. At the end of the experimental schedule, the expression of NF-κB signaling proteins, the formation of NLRP3 inflammasome complex and IL-18; IL-17A expression in the lung were observed using Western blot and RT-PCR. The tissue and serum levels of some proinflammatory cytokines were also studied using ELISA. Mast cell density was also studied using toluidine blue staining procedure. RESULTS: Treatment with IL-27 or IL-28B alone was successful to regulate the expression of NF-κB signaling proteins and NLRP3 complex in some cases but best attenuation was observed in animals who received both IL-27 and IL-28B in combination. In combination, it was successful in down-regulating the expression of p-ERK1/2 and in reducing the accumulation of mast cells in the lung tissue associated with BaP-induced lung carcinogenesis. The impaired PPARγ expression was also reinstated upon combination treatment. CONCLUSION: Altogether, the treatment in combination with IL-27 and IL-28B is an effective regimen to attenuate the ROS/NF-κB/NLRP3 axis associated with BaP-induced lung carcinogenesis.


Assuntos
NF-kappa B
19.
Pest Manag Sci ; 77(1): 285-299, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32696596

RESUMO

BACKGROUND: The viviparous aphid Aphis craccivora Koch (Hemiptera: Aphididae) is a serious threat to the crop yield of Lathyrus sativus L. (Fabaceae), commonly known as grass pea. The synthetic insecticides applied to control this insect pest are not safe for the environment. Hence, it is necessary to find volatile organic compounds (VOCs) from two cultivars [BIO L 212 Ratan (BIO) and Nirmal B-1 (NIR)] of L. sativus plants causing behavioral preference of A. craccivora. RESULTS: The VOCs from undamaged (UD), insect-damaged (ID) [plants on which 50 or 100 adults of A. craccivora were fed for 4 h (ID 50 or ID 100)], and mechanically damaged (MD) plants were identified and quantified by gas chromatography-mass spectrometry and gas chromatography-flame ionization detection analyses, respectively. Total VOCs were higher in ID plants compared to UD plants of each cultivar. However, total VOCs were higher in NIR cultivar compared to BIO cultivar for both UD and ID plants. Benzyl alcohol was predominant in volatile extracts of all treatments. In Y-tube olfactometer bioassays, females showed preference towards volatile extracts of UD, ID, and MD plants of each cultivar compared to the control solvent (CH2 Cl2 ). Insects preferred certain synthetic blends comparable to volatile extracts of UD, ID, and MD plants of each L. sativus cultivar against the control solvent. CONCLUSION: Females preferred a synthetic blend of benzyl alcohol, 1,3-diethylbenzene, thymol, and 1-hexadecene at ratios of 142.49: 62.03:1.18:1 dissolved in 25 µL of CH2 Cl2 in olfactometer bioassays, which could be used in developing lures to control this insect pest.


Assuntos
Afídeos , Lathyrus , Compostos Orgânicos Voláteis , Animais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Compostos Orgânicos Voláteis/análise
20.
Environ Sci Pollut Res Int ; 28(34): 47306-47326, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33893581

RESUMO

Lung cancer is the most aggressive as well as deadly form of cancer and most of the lung cancer cases are involved in direct smoking or passive smoking. Oxidative stress and pulmonary inflammation regulated by some transcription factors like Nrf2, NF-κB etc. play important roles in lung cancer. Various combinations of therapies are currently attributed to lung cancer treatment. A plethora of evidence supports that the consumption of plant-derived foods can prevent chronic diseases like cancer. Leaves of olive (Olea europaea L.) are rich in phenolic compounds which are having antioxidant and anti-inflammatory property. Also, bromelain from pineapple juice and from pineapple stem is a potent anti-inflammatory agent. We took a pragmatic approach to prevent carcinogenesis by supplementing the combination of these two extracts. In this study, we have tried to evaluate the amelioration of various hallmarks associated with benzo(a)pyrene-induced lung carcinogenesis upon the combinatorial treatment of ethanolic olive leaf extract (EOLE) and bromelain. We have studied the role of EOLE in amelioration of BaP-induced oxidative stress in the lung. As several reports of anticancer activity of bromelain are available, we have combined EOLE with bromelain to study their protective role against BaP-mediated lung damage. Changes in DNA integrity, LPO level in lung after EOLE-treated animal were examined. Then, we have evaluated the synergistic role of EOLE and bromelain. We have found that EOLE in combination with bromelain was able to increase the translocation of Nrf2 from cytoplasm to nucleus and decrease the translocation of NF-κB from cytoplasm to nucleus. Combination of treatment also reduced the expression of TNFα, IL-6, and some matrix metalloproteinases in lung tissue. Our findings suggest that EOLE and bromelain can synergistically reduce the BaP-induced lung carcinogenesis associated with inflammation and oxidative stress via regulating the expression of various inflammatory markers and also modulating the activity of pulmonary antioxidant armories.


Assuntos
Neoplasias Pulmonares , Olea , Animais , Antioxidantes , Benzo(a)pireno/toxicidade , Bromelaínas , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Fator 2 Relacionado a NF-E2 , NF-kappa B , Extratos Vegetais/farmacologia , Folhas de Planta
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