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Nine cases of mesenteric desmoid-type fibromatosis were diagnosed and treated in Taizhou Hospital, Wenzhou Medical University between January 2010 and May 2022, including 2 females and 7 males, aged 16 to 59 years. The lesions were in the mesentery of small intestine with 7 cases, ileocecal junction with 1 cases and transverse colon with 1 case. The tumors had an unclear boundary and no envelope, the section was solid, gray and tough. The mean maximum diameter was (10.7±8.5) cm (range 3.5-33.0 cm). Microscopically, fusiform fibroblasts and myofibroblasts were parallel, bunched or staggered, buried in a large amount of extracellular collagen. The cell morphology was relatively consistent, without obvious atypia, and mitosis was rare. Immunohistochemistry showed that the tumor cells were positive for vimentin (9/9), ß-catenin (9/9), while smooth muscle actin (5/9) stains were focally positive. Ki-67 proliferation index was 1%-10%. Cytokeratin Pan, S-100, STAT6, CD117, DOG1, CD34, desmin and anaplastic lymphoma kinase stains were negative. Genetic analysis showed that there were 7 cases of c.121G>A(p.Thr41Ala) mutation of CTNNB1 gene, 1 case of c.121G>A(p.Thr41Ala) and 1 case of c.134C>T(p.Ser45Phe) double mutation, and 1 case of wild type. Tumors were surgically resected in all 9 cases. Eight cases had no recurrence or metastasis, 1 case had recurrence 6 months later, and no recurrence or metastasis after additional surgical resection.
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Fibromatose Agressiva , Masculino , Feminino , Humanos , Fibromatose Agressiva/genética , Fibromatose Agressiva/cirurgia , Fibromatose Agressiva/diagnóstico , Imuno-Histoquímica , Fibroblastos/metabolismo , Mesentério/química , Mesentério/metabolismo , Mesentério/patologia , beta Catenina/genética , beta Catenina/análiseRESUMO
Research on social cognitive ability in domestic cats is limited. The current study investigated social referencing in cats when exposed to first, a solvable, and then, an unsolvable scenario (i.e., reachable and unreachable treats) in the presence of either an attentive or an inattentive caregiver. Cats expressed more gaze alternation (P = 0.013), but less interaction with the caregiver (P = 0.048) and approached the treat container less frequently (P = 0.017) during the unsolvable test, compared to the solvable test. When in the presence of an attentive caregiver, cats initiated first gaze at the caregiver faster (P = 0.001); gazed at the caregiver for longer (P = 0.034); and approached the treat more frequently (P = 0.040), compared to when the caregiver was inattentive. Significant interaction was observed between test and caregiver's attentional state on the expression of sequential behavior, a type of showing behavior. Cats exhibited this behavior marginally more with attentive caregivers, compared to inattentive caregivers, but only during the unsolvable test. There was a decrease in sequential behavior during the unsolvable test, compared to solvable test, but this was only seen with inattentive caregivers (P = 0.018). Our results suggest that gaze alternation is a behavior reliably indicating social referencing in cats and that cats' social communication with humans is affected by the person's availability for visual interaction.
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Atenção , Comunicação , Animais , Gatos , Cognição , Humanos , Habilidades SociaisRESUMO
Tight junctions (TJ) are protein structures that control the transport of water, ions and macromolecules across cell layers. Functions of the transmembrane TJ protein, occluding (OCLN) and the cytoplasmic TJ proteins, tight junction protein 1 (TJP1; also known as zona occludens protein-1), cingulin (CGN) and claudins (CLDN) are reviewed, and current evidence of their role in the ovarian function is reviewed. Abundance of OCLN, CLDNs and TJP1 mRNA changed during follicular growth. In vitro treatment with various growth factors known to affect ovarian folliculogenesis indicated that CGN, OCLN and TJP1 are hormonally regulated. The summarized studies indicate that expression of TJ proteins (i.e., OCLN, CLDN, TJP1 and CGN) changes with follicle size in a variety of vertebrate species but whether these changes in TJ proteins are increased or decreased depends on species and cell type. Evidence indicates that autocrine, paracrine and endocrine regulators, such as fibroblast growth factor-9, epidermal growth factor, androgens, tumor necrosis factor-α and glucocorticoids may modulate these TJ proteins. Additional evidence presented indicates that TJ proteins may be involved in ovarian cancer development in addition to normal follicular and luteal development. A model is proposed suggesting that hormonal downregulation of TJ proteins during ovarian follicular development could reduce barrier function (i.e., selective permeability of molecules between theca and granulosa cells) and allow for an increase in the volume of follicular fluid as well as allow additional serum factors into the follicle that may directly impact granulosa cell functions.
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Permeabilidade da Membrana Celular/efeitos dos fármacos , Folículo Ovariano/citologia , Neoplasias Ovarianas/patologia , Proteínas de Junções Íntimas/metabolismo , Animais , Feminino , Humanos , Folículo Ovariano/metabolismo , Neoplasias Ovarianas/metabolismoRESUMO
Ribonucleotide reductase (RR) catalyzes the reduction of ribonucleotides to deoxyribonucleotides for DNA synthesis. Human RR small subunit M2 exists in a homodimer form. However, the importance of the dimer form to the enzyme and the related mechanism remain unclear. In this study, we tried to identify the interfacial residues that may mediate the assembly of M2 homodimer by computational alanine scanning based on the x-ray crystal structure. Co-immunoprecipitation, size exclusion chromatography, and RR activity assays showed that the K95E mutation in M2 resulted in dimer disassembly and enzyme activity inhibition. In comparison, the charge-exchanging double mutation of K95E and E98K recovered the dimerization and activity. Structural comparisons suggested that a conserved cluster of charged residues, including Lys-95, Glu-98, Glu-105, and Glu-174, at the interface may function as an ionic lock for M2 homodimer. Although the measurements of the radical and iron contents showed that the monomer (the K95E mutant) was capable of generating the diiron and tyrosyl radical cofactor, co-immunoprecipitation and competitive enzyme inhibition assays indicated that the disassembly of M2 dimer reduced its interaction with the large subunit M1. In addition, the immunofluorescent and fusion protein-fluorescent imaging analyses showed that the dissociation of M2 dimer altered its subcellular localization. Finally, the transfection of the wild-type M2 but not the K95E mutant rescued the G1/S phase cell cycle arrest and cell growth inhibition caused by the siRNA knockdown of M2. Thus, the conserved Lys-95 charged residue cluster is critical for human RR M2 homodimerization, which is indispensable to constitute an active holoenzyme and function in cells.
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Ácido Glutâmico/metabolismo , Lisina/metabolismo , Multimerização Proteica , Ribonucleosídeo Difosfato Redutase/metabolismo , Substituição de Aminoácidos , Biocatálise , Proliferação de Células , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Ácido Glutâmico/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Células HeLa , Humanos , Immunoblotting , Lisina/genética , Microscopia Confocal , Modelos Moleculares , Mutação , Interferência de RNA , Ribonucleosídeo Difosfato Redutase/química , Ribonucleosídeo Difosfato Redutase/genéticaRESUMO
A green approach is proposed for in situ growth of porous platinum nanoparticles on graphene oxide (PtNPs/GO). The resulting nanocomposite has been proven to function as peroxidase mimetics that can catalyze the reaction of peroxidase substrate in the presence of hydrogen peroxide. On the basis of the peroxidase-like activity, we used the PtNPs/GO as a signal transducer to develop a colorimetric assay for the direct detection of cancer cells. By using folic acid as a recognition element, a total of 125 cancer cells (MCF-7) can be distinguished by naked-eye observation. We envision that this nanomaterial could be used as a power tool for a wide range of potential applications in biotechnology and medicine.
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Colorimetria , Grafite/química , Nanopartículas Metálicas , Platina/química , Humanos , Microscopia de Força Atômica , Óxidos/químicaRESUMO
This primary objective of our study was to investigate the relationship between serum calcium levels and the occurrence of sudden cardiac arrest (SCA) in stroke patients. We analyzed the clinical data of 10,423 acute stroke patients admitted to the intensive care unit. The association between serum calcium and SCA following an acute stroke was assessed through multivariate logistic regression. We explored the non-linear connection between serum calcium levels and SCA in stroke patients using a generalized additive model and smooth curve fitting. Our study uncovered that serum calcium serves as an independent risk factor for sudden cardiac arrest in stroke patients. Notably, we observed that the relationship between serum calcium levels upon admission and the occurrence of SCA in stroke patients within the hospital was non-linear. Furthermore, we identified inflection points in serum calcium levels at 8.2 and 10.4 mg/dL. These findings emphasize a non-linear relationship between serum calcium levels and the risk of SCA in stroke patients. Maintaining serum calcium within the range of 8.2-10.4 mg/dL could lead to a significant reduction in the incidence of cardiac arrest among stroke patients.
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Parada Cardíaca , Acidente Vascular Cerebral , Humanos , Cálcio , Estudos Retrospectivos , Parada Cardíaca/complicações , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Fatores de Risco , Acidente Vascular Cerebral/complicações , Unidades de Terapia IntensivaRESUMO
TMEM16A, a member of the Transmembrane protein 16 family, serves as the molecular basis for calcium activated chloride channels (CaCCs). We use RT-PCR to demonstrate the expression of TMEM16A in the neurons of Helicoverpa armigera, and records the CaCCs current of acute isolated neurons of H. armigera for the first time using patch clamp technology. In order to screen effective inhibitors of calcium-activated chloride channels, the inhibitory effects of four chloride channel inhibitors, CaCCinh-A01, NPPB, DIDS, and SITS, on CaCCs were compared. The inhibitory effects of the four inhibitors on the outward current of CaCCs were CaCCinh-A01 (10⯵M, 56.31), NPPB (200⯵M, 43.69â¯%), SITS (1â¯mM, 12.41â¯%) and DIDS (1â¯mM, 13.29â¯%). Among these inhibitors, CaCCinh-A01 demonstrated the highest efficacy as a blocker. To further explore whether calcium channel proteins can serve as potential targets of pyrethroids, we compared the effects of (type I) tefluthrin and (type II) deltamethrin on CaCCs. 10⯵M and 100⯵M tefluthrin can stimulate a large tail current in CaCCs, prolonging their deactivation time by 10.44â¯ms and 31.49â¯ms, and the V0.5 shifted in the hyperpolarization by 2-8â¯mV. Then, deltamethrin had no obvious effect on the deactivation and activation of CaCCs. Therefore, CaCCs of H. armigera can be used as a potential target of pyrethroids, but type I and type II pyrethroids have different effects on CaCCs.
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Scratching is a natural behavior in cats but can cause damage to household furnishings. In this work, we sought to identify potential semiochemicals in the urine and feces of domestic cats that may modify cat scratching behavior. Sex differences among adult, intact cats were examined for volatile molecules in their urine (n = 7 females, 7 males) and feces (n = 8 females, 10 males) using gas chromatography-mass spectrometry (GC-MS). Males had seven times more 3-Mercapto-3-Methyl Butanol (MMB, p < 0.001) in the urine and 98% more butanoic acid (p = 0.02) in the feces than females. One mL of mineral oil without (i.e., control) or with MMB (0.1 µg/mL) and butanoic acid (100 µg/mL; i.e., treatment), which corresponds to the estimated biological amount in a single elimination from a male cat, were evaluated for their effectiveness in modifying the use of scratching devices by cats. Two identical cardboard standing scratchers, treated with either the control or the solution containing both semiochemicals delivered through a hanging cotton sock were placed side by side in a home/shelter environment. The preference test consisted of exposing individual cats (n = 28) to both scratchers for 20 min and recording the duration and frequency they interacted or scratched each scratcher. The semiochemical solution significantly decreased scratching time (21.19 ± 3.8 vs. 6.08 ± 3.8 s; p < 0.001) and interaction time (31.54 ± 5.9 vs. 12.90 ± 5.9 s; p = 0.0001) and tended to reduce scratching frequency (1.49 ± 0.3 vs. 0.82 ± 0.3 times; p = 0.07) compared with the control solution. The male-representative solution of MMB and butanoic acid was aversive to cats and might have future applications in protecting furniture from the destructive scratching or in modifying behavior of domestic cats.
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Environmental changes like vet visit could cause stress in cats. Studies have attempted to develop stress management strategies targeting sensory systems. Even though species-appropriate music which includes cat affiliative sound (e.g., cats' purring and suckling sound) has been shown to relieve stress in cats. Little is known whether the cat sound alone works in stress management. This study was conducted to investigate the effects of species-relevant auditory stimuli on stress in cats exposed to a novel environment. During the 28-day experiment periods, 20 cats received four types of sound treatments which included silence (T1), purr of cats (T2), eating sound in cats (T3), and the mixed sound of T2 and T3 (T4) in a novel environment in random orders with intervals of 1 week between treatments. Cats' behaviors were recorded during each 10-min test. Results showed that T4 reduced visual scanning (P = 0.017) without significantly affecting other behaviors, compared with other treatments. Together, the two types of cat-specific sounds did not exert pronounced effects of relieving stress on cats exposed to a novel environment.
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Inappropriate dietary management may lead to delayed recovery from castration surgery and significant weight gain in cats after castration. Wet canned food often exhibits more advantageous characteristics than dry food (e.g., higher palatability and digestibility, and lower energy density). This study compared the effects of canned and dry food on surgical recovery and weight management in cats after castration. Eighteen healthy cats (weighed 4.33 ± 1.04 kg and aged 18-months old) were allocated to one of the two dietary treatments (N = 9/group), dry (CON) and canned food (CAN) balanced for sex and initial BW. Cats were fed ad libitum for 7 weeks, including one week before surgery (week 0) and 6 weeks after surgery (week 1-6). Daily dry matter intake (DMI), and weekly body weight (BW) and body condition score (BCS) was obtained. Feces were collected for measuring nutrient digestibility and concentrations of short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA). Physical pain and wound surface assessment were performed at week 1. Blood was also collected intermittently for measuring biochemical indices and untargeted metabolomics analysis. Results indicated that BW, BCS and daily DMI in CON group increased (P < 0.05) over time after castration, but were maintained relatively stable in CAN group. Cats in CAN group exhibited less pain-related behavior as reflected by lower score of comfort (P < 0.05) and vocalization (P < 0.10), improved wound surface assessment (P < 0.10), lower level of lipase (P < 0.10) and ratio of blood urea nitrogen/serum creatinine (BUN/SC; P < 0.05), and higher level of superoxide dismutase (SOD; P < 0.05) in week 1 than CON cats. Meanwhile, the CAN group had significantly higher concentration of immunoglobulin G (IgG) on days 5 and 7, and higher level of high-density lipoprotein cholesterol (HDL-C; P < 0.10) but lower triglyceride (TG; P < 0.05) than CON group on day 20 and 48. Fecal total and most individual SCFA increased significantly from week 1 to week 6 regardless of diet, but the increase of butyric acid over time only occurred in CON group (P < 0.05). Also, serum metabolomic analysis revealed differential metabolic pathways between the two groups. Overall, compared with the dry food, the canned food tested in our study promoted cat wound recovery by reducing pain and increasing immune and antioxidative capacity after sterilizing surgery, and helped to maintain healthy body condition in cats after castration.
Castration is a surgical operation common in pet cats and dogs, and weight gain is often observed a period after castration. Nutritional management can be important for animal health in both processes. Due to differences in manufacturing techniques and nutrient composition, wet canned food generally exhibits higher palatability and lower energy density than dry food. Till date, few studies have explored if compared to dry kibbles, canned diet can have advantages in promoting recovery from castration surgery and maintaining normal body condition after castration in cats. In our study, dry and canned diets were fed to cats experiencing castration surgery with a free-feeding method. During the one week after surgery, cats fed canned food exhibited less pain and discomfort, and improved inflammation and antioxidative capacity than cats fed dry food. During the four weeks after surgery, cats fed dry food showed significantly more weight gain and change of body condition, meanwhile their blood and fecal measures resembled more of those observed in overweight and/or obese individuals than cats fed canned food. Collectively, canned food with high palatability and low energy density promoted the recovery of cats from the castration surgery and reduced their weight gain after castration.
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Dieta , Ácidos Graxos , Masculino , Gatos , Animais , Peso Corporal , Dieta/veterinária , Fezes/química , Ácidos Graxos/análise , Ácidos Graxos Voláteis , Orquiectomia/veterinária , Ração Animal/análise , DigestãoRESUMO
Transportation is common in cats and often causes stress and intestinal disorders. Antimicrobial peptides (AMPs) exhibit a broad spectrum of antibacterial activity, and they may have the capacity for antioxidant and immune regulation. The objective of this study was to investigate the effects of dietary supplementation with AMPs on stress response, gut microbiota and metabolites of cats that have undergone transport stress. A total of 14 Ragdoll cats were randomly allocated into 2 treatments: basal diet (CON) and a basal diet supplemented with 0.3% AMPs. After a 6-week feeding period, all cats were transported for 3 h and, then, fed for another week. The results show that the diarrhea rate of cats was markedly reduced by supplementation with AMPs throughout the trial period (p < 0.05). In addition, AMPs significantly reduced serum cortisol and serum amyloid A (p < 0.05) and increased apolipoprotein 1 after transportation (p < 0.05). Moreover, AMPs reduced the level of inflammatory factors in the serum caused by transportation stress, including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) (p < 0.05). The AMPs enhanced the activities of glutathione peroxidase (p < 0.01) and superoxide dismutase (p < 0.05). Furthermore, cats fed AMPs had higher levels of branched chain fatty acids (BCFAs) and a relative abundance of Blautia and a lower relative abundance of Negativibacillus after transportation (p < 0.05). The serum metabolome analysis further revealed that AMPs markedly regulated lipid metabolism by upregulating cholic acid expression. In conclusion, AMP supplementation alleviated oxidative stress and inflammatory response in transportation by regulating the gut microbiota and metabolites, thereby relieving stress-induced diarrhea and supporting gut and host health in cats.
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A variety of physical, emotional, and mental factors can induce a stress response in pet dogs and cats. During this process, hypothalamus-pituitary-adrenal (HPA) and sympathetic-adrenal medulla (SAM) axes are activated to produce a series of adaptive short-term reactions to the aversive situations. Meanwhile, oxidative stress is induced where there is an imbalance between the production and scavenging of reactive oxygen species (ROS). Oxidative damage is also incorporated in sustained stress response causing a series of chronic problems, such as cardiovascular and gastrointestinal diseases, immune dysfunction, and development of abnormal behaviors. In this review, the effects and mechanisms of dietary regulation strategies (e.g., antioxidants, anxiolytic agents, and probiotics) on relieving stress in pet dogs and cats are summarized and discussed. We aim to shed light on future studies in the field of pet food and nutrition.
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Dietary changes are inevitable for pets, yet little is known about the impact of different dietary change methods on the gastrointestinal response. The current comparative study evaluated the effects of different dietary changes on the diarrheal symptoms, fecal fermentation characteristics, microbiota, and metabolic profile of healthy puppies. A total of 13 beagle puppies were randomly divided into two groups; puppies in the abrupt change (AC) group were given 260 g of a chicken- and duck-based extruded diet (CD)daily for the one-week transition period, whereas puppies in the gradual transition (GT) group were fed according to a gradual transition ratio of a salmon-based extruded diet (SA) and a CD diets with a difference of 40 g per day for seven consecutive days. Serum samples were collected on D7, and fecal samples were collected on D0 and D7. The results indicated that GT reduced the incidence of diarrhea in puppies throughout the trial period. Dietary change methods had no influence on serum inflammatory factors or fecal SCFAs, but isovaleric acid was significantly reduced after GT. Meanwhile, 16S rRNA sequencing showed that the fecal microbiota was changed after different dietary changes. Compared with the bacterial changes after AC, the relative abundances of beneficial bacteria (i.e., Turicibacter and Faecalibacterium) in feces were increased after GT in puppies. Additionally, both GT and AC caused changes in amino acid metabolism, while AC also altered lipid metabolism. AC increased fecal histamine and spermine concentrations, but decreased concentrations of metabolites such as 5-hydroxyindoleacetic acid and serotonin. Our findings indicated that GT most likely reduced the diarrhea rate in puppies by modulating the composition and metabolism of the gut microbiota.
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Domestic cats are descended from solitary wild species and rely heavily on the olfaction system and chemical signals for daily activities. Cats kept as companion animals may experience stress due to a lack of predictability in their physical or social environment. The olfactory system is intimately connected to the brain regions controlling stress response, thus providing unique opportunities for olfactory strategies to modify stress and related behavioral problems in cats. However, the olfactory intervention of stress in cats has been mainly focused on several analog chemical signals and studies often provide inconsistent and non-replicable results. Supportive evidence in the literature for the potentially effective olfactory stimuli (e.g., cheek and mammary gland secretions, and plant attractants) in treating stress in cats was reviewed. Limitations with some of the work and critical considerations from studies with natural or negative results were discussed as well. Current findings sometimes constitute weak evidence of a reproducible effect of cat odor therapy for stress. The welfare application of an olfactory stimulus in stress alleviation requires a better understanding of its biological function in cats and the mechanisms at play, which may be achieved in future studies through methodological improvement (e.g., experiment pre-registration and appropriate control setting) and in-depth investigation with modern techniques that integrate multisource data. Contributions from individual and environmental differences should be considered for the stress response of a single cat and its sensitivity to olfactory manipulation. Olfactory strategies customized for specific contexts and individual cats can be more effective in improving the welfare of cats in various stressful conditions.
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Softening dry food with water is believed to be more beneficial to the intestinal health and nutrients absorption of dogs by some owners, but there appears to be little scientific basis for this belief. Thus, this study aimed to compare feeding dry food (DF) and water-softened dry food (SDF) on stress response, intestinal microbiome, and metabolic profile in dogs. Twenty healthy 5-month-old beagle dogs were selected and divided into two groups according to their gender and body weight using a completely randomized block design. Both groups were fed the same basal diet, with one group fed DF and the other fed SDF. The trial lasted for 21 days. The apparent total tract digestibility (ATTD) of nutrients, inflammatory cytokines, stress hormones, heat shock protein-70 (HSP-70), fecal microbiota, short-chain fatty acids (SCFAs), branch-chain fatty acids (BCFAs), and metabolomics were measured. Results showed that there was no significant difference in body weight, ATTD, and SCFAs between the DF and SDF groups (p > 0.05), whereas feeding with SDF caused a significant increase in serum cortisol level (p < 0.05) and tended to have higher interleukin-2 (p = 0.062) and HSP-70 (p = 0.097) levels. Fecal 16S rRNA gene sequencing found that the SDF group had higher alpha diversity indices (p < 0.05). Furthermore, the SDF group had higher levels of Streptococcus, Enterococcus, and Escherichia_Shigella, and lower levels of Faecalibacterium (p < 0.05). Serum and fecal metabolomics further showed that feeding with SDF significantly influenced the purine metabolism, riboflavin metabolism, and arginine and proline metabolism (p < 0.05). Overall, feeding with SDF caused higher cortisol level and generated effects of higher intestinal microbial diversity in dogs, but it caused an increase in some pathogenic bacteria, which may result in intestinal microbiome disturbance and metabolic disorder in dogs. In conclusion, feeding with SDF did not provide digestive benefits but caused some stress and posed a potential threat to the intestinal health of dogs. Thus, SDF is not recommended in the feeding of dogs.
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Methylsulfonylmethane (MSM) is a natural sulfur-containing organic substance that has many biological functions, such as antioxidant, anti-inflammatory, skin nourishing, and hair growth-promoting effects. This study was conducted to determine the effect of MSM supplementation on growth performance, antioxidant capacity, and hair quality in kittens. A total of 21 Ragdoll kittens were assigned to three diets by initial body weight and gender: basal diet supplemented with 0%, 0.2%, and 0.4% MSM (CON, LMSM, and HMSM groups) for 65 days. During the whole period, the food intake of kittens in the MSM-treated groups tended to be higher (P < 0.10) compared with the CON group, and the average daily gain (ADG) had no significant difference when compared to the kittens in the CON group (P > 0.05). Antioxidant capacity had no significant difference (P > 0.05) among the groups. The scale thickness of hair tended to be smaller in the LMSM group compared to the CON group (P < 0.10) and decreased significantly (P < 0.05) over time from d 0 to d 65 in the LMSM group, indicating the improvement of hair quality. Besides, supplementation with LMSM increased bacterial diversity. Kittens fed MSM had no significant differences in fecal genus at the end of the study. No significant differences in fecal short-chain fatty acids were observed among groups. Fecal metabolomics analysis further revealed that MSM hardly affected the metabolites. Overall, dietary supplementation with 0.2% MSM can improve the hair quality of kittens. Furthermore, 0.2â¼0.4% of MSM had no detrimental effects on serum biochemistry, growth performance, gut microbiota, and metabolome, which supports the safety inclusion of MSM to a certain degree in feline diets. To the best of our knowledge, this is the first study to investigate the effects of MSM supplementation in cats.
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The induction of immunogenic cell death (ICD) is an attractive strategy for generating in situ autologous tumor cell-based vaccines and thus has great potential in cancer prevention and personalized immunotherapy. However, the effectiveness of ICD in tumor immunotherapy has been greatly limited, mainly by low induction efficiency and the immunosuppressive tumor microenvironment (TME). Herein, we report a new strategy for chemo-photothermal therapy-induced ICD by employing photothermal MnO2 nanoparticles loaded with doxorubicin (DOX) in tumor immunotherapy to overcome the low efficiency of traditional ICD inducers and the immunosuppressive TME. Specifically, we prepared photothermal bovine serum albumin (BSA)-templated MnO2 NPs (BSA/MnO2 NPs) with good aqueous dispersibility and high biocompatibility through the direct reduction of KMnO4 with BSA, and we then efficiently loaded DOX, an ICD inducer, onto the MnO2 NPs through coordination (DOX-BSA/MnO2 NPs). The DOX-BSA/MnO2 NPs achieved high photothermal conversion efficiency, highly efficient tumor targeting, TME-responsive DOX release and modulation of the hypoxic TME. Notably, a marked in vivo synergistic therapeutic effect was achieved in a triple-negative breast carcinoma-bearing mouse model by combining chemo-photothermal therapy-induced ICD with amelioration of the immunosuppressive TME. Our research highlights the great promise of modulating the TME with photothermal MnO2 nanosystems to enhance ICD-induced antitumor immunotherapy.
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Morte Celular Imunogênica , Nanopartículas , Animais , Doxorrubicina/farmacologia , Imunoterapia , Compostos de Manganês/farmacologia , Camundongos , Óxidos/farmacologia , Fototerapia , Terapia Fototérmica , Microambiente TumoralRESUMO
Early-life exposure to environmental stress disrupts the gut barrier and leads to inflammatory responses and changes in gut microbiota composition. Gallic acid (GA), a natural plant polyphenol, has received significant interest for its antioxidant, anti-inflammatory, and antimicrobial properties that support the maintenance of intestinal health. To assess whether dietary supplementation of GA alleviates environmental stress, a total of 19 puppies were randomly allocated to the following three dietary treatments for 2 weeks: 1) basal diet (control (CON)); 2) basal diet + transportation (TS); and 3) basal diet with the addition of 500 mg/kg of GA + transportation (TS+GA). After a 1-week supplementation period, puppies in the TS and TS+GA groups were transported from a stressful environment to another livable location, and puppies in the CON group were then left in the stressful environment. Results indicated that GA markedly reduced the diarrhea rate in puppies throughout the trial period and caused a moderate decline of serum cortisol and HSP-70 levels after transportation. Also, GA alleviated the oxidative stress and inflammatory response caused by multiple environmental stressors. Meanwhile, puppies fed GA had a higher abundance of fecal Firmicutes and Lactobacillus and lower Proteobacteria, Escherichia-Shigella, and Clostridium_sensu_stricto_1 after transportation. As a result, the TS+GA group had the highest total short-chain fatty acids and acetic acid. Also, the fecal and serum metabolomics analyses revealed that GA markedly reversed the abnormalities of amino acid metabolism, lipid metabolism, carbohydrate metabolism, and nucleotide metabolism caused by stresses. Finally, Spearman's correlation analysis was carried out to explore the comprehensive microbiota and metabolite relationships. Overall, dietary supplementation of GA alleviates oxidative stress and inflammatory response in stressed puppies by causing beneficial shifts on gut microbiota and metabolites that may support gut and host health.
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Antioxidantes/farmacologia , Ácido Gálico/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Microbiota/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Fatores Etários , Ração Animal , Animais , Biomarcadores , Cães , Meio Ambiente , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Cromatografia Gasosa-Espectrometria de Massas , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolômica/métodos , Metagenoma , Metagenômica/métodos , RNA Ribossômico 16SRESUMO
The size of an organ must be tightly controlled so that it fits within an organism. The mammalian lens is a relatively simple organ composed of terminally differentiated, amitotic lens fiber cells capped on the anterior surface by a layer of immature, mitotic epithelial cells. The proliferation of lens epithelial cells fuels the growth of the lens, thus controling the size of the lens. We report that the Notch signaling pathway defines the boundary between proliferation and differentiation in the developing lens. The loss of Notch signaling results in the loss of epithelial cells to differentiation and a much smaller lens. We found that the Notch effector Herp2 is expressed in lens epithelium and directly suppresses p57Kip2 expression, providing a molecular link between Notch signaling and the cell cycle control machinery during lens development.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Regulação da Expressão Gênica , Cristalino , Receptores Notch/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais/fisiologia , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Células COS , Ciclo Celular/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células , Chlorocebus aethiops , Inibidor de Quinase Dependente de Ciclina p57/genética , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina , Hibridização In Situ , Cristalino/anatomia & histologia , Cristalino/fisiologia , Camundongos , Camundongos Knockout , Fenótipo , Receptores Notch/genética , Proteínas Repressoras/genéticaRESUMO
Ubiquitin-like with plant homeodomain and really interesting new gene finger domains 1 (UHRF1) is a multi-domain nuclear protein that plays an important role in epigenetics and tumorigenesis, but its role in normal ovarian follicle development remains unknown. Thus, the present study evaluated if UHRF1 mRNA abundance in bovine follicular cells is developmentally and hormonally regulated, and if changes in UHRF1 are associated with changes in DNA methylation in follicular cells. Abundance of UHRF1 mRNA was greater in granulosa cells (GC) and theca cells (TC) from small (<6 mm) than large (≥8 mm) follicles and was greater in small-follicle GC than TC. In GC and TC, fibroblast growth factor 9 (FGF9) treatment increased (P < 0.05) UHRF1 expression by 2-fold. Also, luteinizing hormone (LH) and insulin-like growth factor 1 (IGF1) increased (P < 0.05) UHRF1 expression in TC by 2-fold, and forskolin (an adenylate cyclase inducer) alone or combined with IGF1 increased (P < 0.05) UHRF1 expression by 3-fold. An E2F transcription factor inhibitor (E2Fi) decreased (P < 0.05) UHRF1 expression by 44% in TC and by 99% in GC. Estradiol, progesterone, and dibutyryl-cAMP decreased (P < 0.05) UHRF1 mRNA abundance in GC. Treatment of GC with follicle-stimulating hormone (FSH) alone had no effect but when combined with IGF1 enhanced the UHRF1 mRNA abundance by 2.7-fold. Beauvericin (a mycotoxin) completely inhibited the FSH plus IGF1-induced UHRF1 expression in small-follicle GC. Treatments that increased UHRF1 mRNA (i.e., FGF9) in GC tended to decrease (by 63%; P < 0.10) global DNA methylation, and those that decreased UHRF1 mRNA (i.e., E2Fi) in GC tended to increase (by 2.4-fold; P < 0.10) global DNA methylation. Collectively, these results suggest that UHRF1 expression in both GC and TC is developmentally and hormonally regulated, and that UHRF1 may play a role in follicular growth and development as well as be involved in ovarian epigenetic processes.