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1.
Vet Sci ; 11(8)2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39195827

RESUMEN

Bovine viral diarrhea virus (BVDV) is an RNA virus associated with severe economic losses in animal production. Effective vaccination and viral surveillance are urgent for the prevention and control of BVDV infection. However, the application of traditional modified live vaccines and inactivated vaccines is faced with tremendous challenges. In the present study, we describe the preclinical efficacy of two BVDV mRNA vaccines tested in mice and guinea pigs, followed by a field trial in goats, where they were compared to a commercial vaccine (formaldehyde inactivated). The two mRNAs were engineered to express the envelope protein E2 of BVDV-1, the most prevalent subtype across the world, through a 5' cap-dependent or independent fashion. Better titers of neutralizing antibodies against BVDV-1 were achieved using the capped RNA in the sera of mice and guinea pigs, with maximum values reaching 9.4 and 13.7 (by -log2), respectively, on the 35th day post-vaccination. At the same time point, the antibody levels in goats were 9.1 and 10.2 for the capped and capless RNAs, respectively, and there were no significant differences compared to the commercial vaccine. The animals remained healthy throughout the experiment, as reflected by their normal leukogram profiles. Collectively, our findings demonstrate that mRNA vaccines have good safety and immunogenicity, and we laid a strong foundation for the further exploitation of efficient and safe BVDV vaccines.

2.
Animals (Basel) ; 14(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38791685

RESUMEN

Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.

3.
Vet Radiol Ultrasound ; 65(4): 385-391, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38613764

RESUMEN

Hyperadrenocorticism is an uncommon but important endocrine disease in guinea pigs, but due to its subtle clinical signs and the limited information in veterinary literature, it can be underdiagnosed or misdiagnosed. Ultrasound of the adrenal glands in patients with suspected hyperadrenocorticism can help in identifying adrenomegaly. The purpose of this prospective study was to identify ultrasonographic adrenal gland dimensions in presumed healthy guinea pigs using the same standardized method described for dogs and cats. A conscious ultrasound scan was conducted on twenty client-owned, presumed healthy guinea pigs, and their adrenal glands were measured. A possible correlation between adrenal dimensions with age, sex, and body weight was investigated. The mean length, cranial and caudal pole thickness for the left and right adrenal glands were, respectively, 12.64 ± 2.11 mm and 11.55 ± 1.52 mm; 4.83 mm ± 1.03 mm and 4.69 ± 1.34 mm; 4.8 ± 1.23 mm and 4.04 ± 0.75 mm. The thickness of the left caudal pole was significantly higher than the right (P = 0.02). A significant positive correlation was found between the length of the left adrenal gland and both age (r = 0.46; P = .03) and weight (r = 0.59; P = .01). Statistical correlation between the thickness of each cranial and caudal pole, with age, sex, or weight, was not found. The dimensions provided could prove a useful tool in the clinical evaluation of guinea pigs with suspected hyperadrenocorticism.


Asunto(s)
Glándulas Suprarrenales , Ultrasonografía , Animales , Cobayas/anatomía & histología , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/anatomía & histología , Ultrasonografía/veterinaria , Femenino , Masculino , Estudios Prospectivos , Valores de Referencia
4.
Regul Toxicol Pharmacol ; 149: 105617, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38561146

RESUMEN

Accumulating evidence has shown that the abnormal toxicity test (ATT) is not suitable as a quality control batch release test for biologics and vaccines. The purpose of the current study was to explore the optimal ATT experimental design for an adenoviral vector-based vaccine product to avoid false positive results following the standard test conditions stipulated in the Pharmacopoeias. ATT were conducted in both mice and guinea pigs based on methods in Pharmacopeias, with modifications to assess effects of dose volume and amount of virus particles (VPs). The results showed intraperitoneal (IP) dosing at human relevant dose and volume (i.e., VPs), as required by pharmacopeia study design, resulted in false positive findings not associated with extraneous contaminants of a product. Considering many gene therapy products use adeno associated virus as the platform for transgene delivery, data from this study are highly relevant in providing convincing evidence to show the ATT is inappropriate as batch release test for biologics, vaccine and gene therapy products. In conclusion, ATT, which requires unnecessary animal usage and competes for resources which otherwise can be spent on innovative medicine research, should be deleted permanently as batch release test by regulatory authorities around the world.


Asunto(s)
Vectores Genéticos , Pruebas de Toxicidad , Animales , Cobayas , Pruebas de Toxicidad/métodos , Ratones , Reacciones Falso Positivas , Femenino , Adenoviridae/genética , Masculino , Vacunas
5.
Animals (Basel) ; 14(7)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38612368

RESUMEN

Biowaste from slaughterhouses can be recovered to benefit food security and reduce contamination potential. More than 3 billion heads of livestock are consumed worldwide, which will increase by 17% by 2028, generating more biowaste, increasing infectious agents, and causing economic losses due to circular economy principles not being applied. This work evaluated the nutritional quality of four types of biowaste from bovine slaughter which were transformed into a meal for guinea pigs (rumen content (RCM), ears (EaM), blood (BM), and cheeks (CM)) according to their chemical composition, digestible components, energy contribution, and voluntary consumption. For the animal model, adult male guinea pigs were arranged in metabolic cages for feces collection without urinary contamination. Nine guinea pigs were used in each digestibility test. First, a direct digestibility test was conducted using a meal of barley as a reference diet (RD), the indigestibility coefficient of which allowed for the estimation of the digestibility of biowaste meals through indirect calculations; for this, diets composed of 80% of the RD and 20% of the corresponding biowaste meals were evaluated. The difference method was suitable for determining the digestibility of beef biowaste using the indigestibility coefficients of the reference diet to calculate the digestibility of ingredients which could not be offered as 100% of the meal but were incorporated as 20%. The digestible protein and metabolizable energy contents of RCM, EaM, BM, and CM were 10.2% and 2853 kcal/kg, 44.5% and 3325 kcal/kg, 70.7% and 2583 kcal/kg, and 80.8% and 3386 kcal/kg, respectively. The CM and BM feeds had the highest contributions of digestible protein due to their higher nitrogen content, and the CM and EaM feeds had the highest ME contents due to their higher fat contents. The biowaste meal consumption in descending order was CM > RCM > EaM > BM, which were consumed without problems. These results are indicative that these components can be part of guinea pigs' diets, and it is recommended to continue studies into guinea pig growth and fattening diets with different levels of these biowaste meals.

6.
Emerg Infect Dis ; 30(5): 1004-1008, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38666640

RESUMEN

We evaluated the in vitro effects of lyophilization for 2 vesicular stomatitis virus-based vaccines by using 3 stabilizing formulations and demonstrated protective immunity of lyophilized/reconstituted vaccine in guinea pigs. Lyophilization increased stability of the vaccines, but specific vesicular stomatitis virus-based vaccines will each require extensive analysis to optimize stabilizing formulations.


Asunto(s)
Modelos Animales de Enfermedad , Liofilización , Estomatitis Vesicular , Vacunas Virales , Animales , Cobayas , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Estomatitis Vesicular/inmunología , Estomatitis Vesicular/prevención & control , Estomatitis Vesicular/virología , Vesiculovirus/inmunología , Vesiculovirus/genética , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Eficacia de las Vacunas , Virus de la Estomatitis Vesicular Indiana/inmunología
7.
Chem Biol Interact ; 395: 111001, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38641146

RESUMEN

In recent years, various poisoning incidents have been reported, involving the alleged use of the so-called Novichok agents, resulting in their addition to the Schedule I list of the Organisation for the Prohibition of Chemical Warfare (OPCW). As the physicochemical properties of these agents are different from the 'classical' nerve agents, such as VX, research is needed to evaluate whether and to what extent existing countermeasures are effective. Here, we evaluated the therapeutic potential of RSDL® (Reactive Skin Decontamination Lotion Kit) for the neutralization of percutaneous toxicity caused by Novichok agents, both in vitro and in vivo. Experiments showed the three selected Novichok agents (A230, A232, A234) could be degraded by RSDL lotion, but at a different rate. The half-life of A234, in the presence of an excess of RSDL lotion, was 36 min, as compared to A230 (<5 min) and A232 (18 min). Following dermal exposure of guinea pigs to A234, application of the RSDL kit was highly effective in preventing intoxication, even when applied up until 30 min following exposure. Delayed use of the RSDL kit until the appearance of clinical signs of intoxication (3-4 h) was not able to prevent intoxication progression and deaths. This study determines RSDL decontamination as an effective treatment strategy for dermal exposure to the Novichok agent A234 and underscores the importance of early, forward use of skin decontamination, as rapidly as possible.


Asunto(s)
Descontaminación , Agentes Nerviosos , Piel , Animales , Cobayas , Descontaminación/métodos , Piel/efectos de los fármacos , Agentes Nerviosos/toxicidad , Agentes Nerviosos/química , Crema para la Piel/farmacología , Crema para la Piel/química , Masculino , Sustancias para la Guerra Química/toxicidad
8.
Biologicals ; 86: 101764, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38537360

RESUMEN

Leptospira interrogans serovar Hardjo is a long slender bacterium of size 0.1-0.3 µm × 5-50 µm. It is one of the major causes of bovine leptospirosis and is of economical importance because of the reproductive failure, still birth, abortion, and reduced productivity in cattle. It is also a zoonotic disease-causing infection in humans characterized by headaches, fever, chills, sweats and myalgia, lethargy, aching joints, pulmonary haemorrhages, and death in severe cases. Control of the disease involves antibiotic therapy, management and vaccination, of which immunization is the cheapest and effective means of disease prevention. The present study was developed to isolate and characterize the outer membrane vesicles of Leptospira interrogans serovar Hardjo and to evaluate their vaccine potential in guinea pig model. The OMVs were isolated from the culture by sonication and ultracentrifugation. In transmission electron microscopy, the isolated OMVs appeared as small spherical structures of 50-200 nm size. In Western blot and indirect ELISA, antibodies specific to OMVs were observed as indicative of a good humoral immune response elicited by L. interrogans serovar Hardjo OMV. The OMV-based Leptospira vaccine was able to prevent kidney lesions and renal colonization compared to the control and bacterin vaccinated group as proven by histopathology and PCR.


Asunto(s)
Vacunas Bacterianas , Leptospirosis , Animales , Cobayas , Leptospirosis/prevención & control , Leptospirosis/inmunología , Leptospirosis/microbiología , Vacunas Bacterianas/inmunología , Modelos Animales de Enfermedad , Leptospira interrogans/inmunología , Membrana Externa Bacteriana/inmunología , Membrana Externa Bacteriana/metabolismo , Femenino , Nanovacunas
9.
Saudi Pharm J ; 32(4): 101992, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38435847

RESUMEN

Total extract of Tephrosia purpurea (T. purpurea) expressed potent ex-vivo bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of T. purpurea total extract (TPTE) using liquid-liquid technique followed by ex-vivo bronchodilator testing indicated that the activity was trapped to the chloroform (CHCl3) soluble fraction. Phytochemical study of the CHCl3 fraction guided by ex-vivo bronchodilator activity led to the isolation of 7 active flavones of which compounds 1 (epi-Tephroapollin G), 3 (Acetyltephroapollin C), 4 (4''-Dehydroxytephroapollin E), and 5 (epi-Tephroapollin F) were new. Structures were identified using relevant spectroscopic tools including optical rotations and CD data. Compounds 1, 3, 4 and lanceolatin A (6) behaved like papaverine by inhibiting carbachol (CCh) as well as high potassium (K+)-mediated contractions at equivalent concentrations with varied potencies whereas (-)-Tephroapollin G (2) selectively inhibited CCh-mediated contractions but was not found active against high K+. epi-Tephroapollin F (5) and (-)-Pseudosemiglabrin (7) in contrast were significantly more potent to abolish CCh induced contraction when compared with high K+ similar to dicyclomine. Papaverine like dual phosphodiesterase enzyme Ca++ ion inhibitory activities of 1, 3, 4 and 6 were confirmed indirectly by the bolster of the isoprenaline curves against CCh to the left whereas Ca++ inhibitory effect of 1 and 3-7 was confirmed by the rightward deflection of Ca++ concentration-response curves (CRCs) towards right with quashing of the maximum response in same fashion like verapamil. Moreover, compounds 2, 5 and 7 at lower concentrations showed selective blockade of muscarinic receptor similar to atropine. Oral administration of the TPTE, CHCl3 and 7 to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol in vivo.

10.
Heliyon ; 10(3): e25226, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38352743

RESUMEN

Lymphadenitis is a commonly occurring and contagious disease in guinea pigs caused by different pathogens, including Streptococcus sp., Staphylococcus sp., and Corynebacterium sp. This study aimed to characterize the bacteria isolated from pus extracted from abscessed mandibular lymph nodes of diseased guinea pigs in Ecuador in 2019 and evaluate the in vitro antibacterial activity of the total extracts of three plant species. Isolates were recovered from three diseased guinea pigs with Lymphadenitis on a farm in Imbabura, Ecuador province. The bacteria were characterized through microbiological, biochemical, and molecular tests as Streptococcus equi subsp. zooepidemicus. Furthermore, the susceptibility of S. equi subsp. zooepidemicus to three plant extracts belonging to the Asteraceae family, Acmella ciliata, Bidens andicola, and Gazania splendens collected in Ecuador, were assessed in vitro by the microdilution method. Our data indicate that all the evaluated extracts showed activity, with a Minimum Inhibitory Concentration (MIC) of 22.50 mg/mL for Acmella ciliata, 11.25 mg/mL for Bidens andicola, and 5.60 mg/mL for Gazania splendens. Bidens andicola extract showed the highest efficacy with a % inhibition of 63.90 at the highest tested concentration (45 mg/mL). This is the first report on the bioactivity of these plant species against S. equi subsp. zooepidemicus.

11.
Stem Cell Res Ther ; 15(1): 46, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365799

RESUMEN

BACKGROUND: Radiotherapy in head and neck cancer management causes degeneration of the salivary glands (SG). This study was designed to determine the potential of gingival mesenchymal stem cells (GMSCs) as a cell-based therapy to regenerate irradiated parotid SG tissues and restore their function using a murine model. METHODS: Cultured isolated cells from gingival tissues of 4 healthy guinea pigs at passage 3 were characterized as GMSCSs using flow cytometry for surface markers and multilineage differentiation capacity. Twenty-one Guinea pigs were equally divided into three groups: Group I/Test, received single local irradiation of 15 Gy to the head and neck field followed by intravenous injection of labeled GMSCs, Group II/Positive control, which received the same irradiation dose followed by injection of phosphate buffer solution (PBS), and Group III/Negative control, received (PBS) injection only. Body weight and salivary flow rate (SFR) were measured at baseline, 11 days, 8-, 13- and 16-weeks post-irradiation. At 16 weeks, parotid glands were harvested for assessment of gland weight and histological and immunohistochemical analysis. RESULTS: The injected GMSCs homed to degenerated glands, with subsequent restoration of the normal gland histological acinar and tubular structure associated with a significant increase in cell proliferation and reduction in apoptotic activity. Subsequently, a significant increase in body weight and SFR, as well as an increase in gland weight at 16 weeks in comparison with the irradiated non-treated group were observed. CONCLUSION: The study provided a new potential therapeutic strategy for the treatment of xerostomia by re-engineering radiated SG using GMSCs.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Ratones , Animales , Cobayas , Modelos Animales de Enfermedad , Glándulas Salivales , Inyecciones Intravenosas , Peso Corporal
12.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1022707

RESUMEN

Objective To investigate the effect of blue light on the dioptric development of the eyes of lens-induced myopia(LIM)guinea pigs.Methods Three-week-old trichromatic guinea pigs were randomly divided into three groups:control group,white light LIM(WL)group,and blue light LIM(BL)group(420 nm LED light,with an illuminance of 700 lx);guinea pigs in the latter two groups wore-10.00 D lenses in their right eyes to induce myopia.All guinea pigs under-went a 12 h light/12 h dark treatment cycle.Before and 2,4 weeks after the intervention,the diopter,axial length,retinal thickness and choroidal thickness were measured in all groups.After 4 weeks of intervention,the corneal fluorescent stai-ning and retinal Hematoxylin and Eosin(HE)staining were conducted.Results Compared with the control group,from week 0 to week 2 of the intervention(changes in weeks 0-2),the eyes in the WL group drifted(-2.22±1.28)D towards myopia,the axial length lengthened by(0.40±0.05)mm,and the retinal and choroidal thicknesses reduced by(-7.42± 7.04)μm and(-6.29±4.66)μm,respectively;compared with the WL group,in the BL group,the eyes drifted toward hyperopia by(0.48±1.16)D,the axial length increased by(0.20±0.10)mm,and retinal and choroidal thicknesses in-creased by(1.36±7.46)μm and(8.05±8.08)μm,respectively(all P<0.05).From week 2 to week 4(changes in weeks 2-4),compared with the control group,the diopter in the WL and BL groups progressed towards myopia,with changes of(-4.64±0.50)D and(-2.11±2.02)D,respectively(both P<0.05);the axial length lengthened,and reti-nal and choroidal thicknesses reduced in the WL group,with changes of(0.44±0.06)mm,(-7.35±5.87)μm and(-4.84±2.61)μm,while the choroidal thickness and the retinal thickness decreased in the BL group,with changes of(-0.33±5.95)μm and(-4.78±4.96)μm,respectively.Observations of corneal fluorescence staining and retinal HE staining indicated that prolonged blue light exposure could lead to damage to corneal and retinal cells.Conclusion Blue light may influence the development of myopia through choroid-related mechanisms,but its inhibitory effect is not positive-ly correlated with time.Prolonged exposure to blue light can damage the cornea and retina,thereby reducing the inhibitory effect.

13.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1022844

RESUMEN

Objective:To study the distribution and changes of dopamine transporter (DAT) in guinea pig eyes under different light patterns.Methods:Thirty-six 3-week-old white ordinary-grade guinea pigs were randomly selected and divided into groups of 10 000 lx, 5 000 lx, and 500 lx, with 12 guinea pigs in each group exposed to strong light, medium strong light, and normal light, respectively.Each group was randomly divided into 3 subgroups, with 4 guinea pigs in each subgroup.The 3 subgroups of 500 lx group received light exposure for 5, 20, and 40 minutes, respectively.The 3 subgroups of 5 000 lx group received light exposure for 2, 4, and 40 minutes, respectively.The 3 subgroups of 10 000 lx group received light exposure for 2, 5, and 20 minutes, respectively.After light treatment, each group of guinea pigs was injected with 99mTc-TRODAT-1 for SPECT DAT imaging, and image data were collected by Micro-SPECT.The region of interest (ROI) of guinea pig retinas was analyzed using Micro-CT software.The counts of ROI were expressed as Sum, which reflected the relative distribution or density of DAT.The DAT density between experimental and control eyes of guinea pigs after light exposure, the differences in DAT density between guinea pig eyes under different light intensities, the differences in DAT density between guinea pig eyes after different light durations, and the cumulative and interactive effects of light intensity and light duration on DAT aggregation in guinea pigs were compared.Another 3 guinea pigs were selected, and after light exposure, the 3 guinea pigs' eyes underwent continuous image acquisition for 6 hours at 20-minute intervals, and 18 images per guinea pig were acquired to analyze the trend of DAT density in guinea pig eyes over time.This study was approved by the Ethics Committee of Shanghai General Hospital (No.2020SQ196). Results:The DAT density (Sum value) of experimental eyes at 500, 5 000, and 10 000 lx were 5 598.97±3 159.38, 8 636.78±2 503.16, and 7 407.39±2 053.41, respectively, significantly higher than 4 388.89±2 902.90, 5 981.92±3 057.44, and 5 091.32±2 039.36 of control eyes ( t=5.31, 4.69, 11.80; all at P<0.001). At 500 lx, there was a statistically significant difference in DAT density between the experimental and control eyes of guinea pigs at different light exposure durations ( F=14.01, P<0.01), while no significant difference was found at other light intensities at different light exposure durations (both at P>0.05). When the light exposure time was 5 minutes, the difference in DAT density between the experimental and control eyes of guinea pigs was significantly greater in the 10 000 lx group than in the 500 lx group ( t=-13.22, P<0.001). There was no statistically significant difference between different groups at other light exposure durations (all at P>0.05). No cumulative or interactive effects of light intensity and light duration were found on the differences in DAT density (all at P>0.05). Continuous scanning after illumination showed that DAT density in guinea pig retinas first increased to a peak over time and then gradually returned to normal values. Conclusions:Light, even under moderate or normal light levels, can cause an increase in the secretion of DAT in the retina and stimulate the production of DAT.Light intensity and duration have no cumulative or interactive effects on the distribution and density of retinal DAT.

14.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1022845

RESUMEN

Objective:To investigate the alteration of m6A demethylase AlkB homolog 5 (ALKBH5) expression and its impact on form-deprivation myopia (FDM) retina in guinea pigs.Methods:Thirty normal SPF grade 3-week-old tricolor guinea pigs were randomly divided into normal control group and experimental group, with 15 in each group.In the experimental group, the right eyes were covered as FDM group and the left eyes uncovered were set as self-control group.Ocular biometry was performed at one-week intervals from baseline to week 4 of the experiment.Spherical equivalent was detected by streak retinoscopy and axial length was measured by A-scan ultrasonography.Animals were sacrificed after 4 weeks of modeling.The distribution and expression of ALKBH5 protein in the guinea pig retina was detected by immunohistochemical and immunofluorescence staining.Expression of ALKBH5 mRNA and protein in guinea pig retina was detected by real-time fluorescence quantitative PCR and Western blot, respectively.The use of animals in ophthalmic and vision research followed the tenets of Animal Research in Vision and Ophthalmology, and the study was approved by the Ethics Committee of North Sichuan Medical College (No.2023087).Results:At weeks 2, 3, and 4 after myopia induction, diopters and axial lengths were significantly higher in the FDM group than in the normal control group and the self-control group (all at P<0.001). Immunohistochemistry and immunofluorescence assays showed that ALKBH5 protein was expressed in the retinal nerve fiber layer, rod/cone photoreceptor cells, and retinal pigment epithelium (RPE) layer, and was highly expressed in the retinal nerve fiber layer and RPE layer.The relative ALKBH5 immunofluorescence intensity in the normal control group, self-control group and FDM group was 1.000±0.204, 0.874±0.076 and 0.571±0.053, respectively, which was lower in the FDM group than in the normal control and self-control groups, showing statistically significant differences ( t=4.069, P=0.006; t=5.176, P=0.014). After 4 weeks of modeling, ALKBH5 mRNA and protein expressions were significantly lower in FDM group than in normal control and self-control groups (both at P<0.01). Conclusions:The expression of m6A demethylase ALKBH5 is decreased in the retina of FDM guinea pigs, suggesting that ALKBH5 and related m6A methylation modification may be involved in the development and progression of myopia.

15.
International Eye Science ; (12): 1207-1212, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1038531

RESUMEN

AIM: To avoid the problem of retinal dissection in guinea pig large eyeball tissue sections, different methods were used to optimize the fixation effect of the posterior pole of the eyeball.METHODS: A total of 75 normal guinea pigs(2 weeks old)were randomly divided into 5 large groups. Group A(1-3 small groups), the entire eyeball was fixed with FAS, Davidson fixative 1(D1), and Davidson fixative 2(D2)for 24 h; group B(4-6 small groups), the entire eyeball was fixed with FAS, D1, and D2 for 1 h, then cut the cornea and fix it in their respective fixatives for 2 h; group C(7-9 small groups), the eyeball was fixed in FAS, D1, and D2 for 1 h, divided into left and right halves along the direction of the optic nerve, and then placed them in their respective fixation solutions for 2 h; group D(10-12 small groups), after fixation for 3 h in FAS, D1, and D2, the eyeball was divided into left and right halves along the optic nerve direction; group E(13-15 small groups), the cornea was cut after fixation for 3 h in FAS, D1, and D2. Hematoxylin-eosin(HE)staining was used to compare the fixation effect on posterior eyeball in each group.RESULTS: After fixation, the surface of the eyeballs in groups, 1-6 and 11-15 was smooth and round, with a transparent and bright color. In groups 7-10, the eyeballs were sunken, wrinkled, and deformed. The HE staining showed that the eyeball morphology of groups 1, 5, 6, 14, and 15 was significantly better than the other groups, with a regular internal tissue structure. The eyeballs of the other groups were sunken and wrinkled, and the internal tissue was curled and tangled, with severe retinal detachment. In groups 1, 5, 6, 14, and 15, the retina, choroid, and sclera tissues of group 14 were closely connected, without obvious retinal detachment, rupture, or curling. The tissue structure was clear and visible, and the cells were arranged neatly.CONCLUSION: The fixation effect of cutting the cornea after fixing guinea pig eyeball with D1 fixative for 3 h is the most ideal, and this operation method is simple and suitable for studying the related structures of the posterior pole of the eye.

16.
Pharmaceutics ; 15(12)2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38140098

RESUMEN

CPZEN-45 is a novel compound with activity against drug-susceptible and drug-resistant tuberculosis (TB). The present study was undertaken to determine the best dose and dosing regimen of inhalable CPZEN-45 powders to use in efficacy studies with TB-infected guinea pigs. The disposition of CPZEN-45 after intravenous, subcutaneous (SC), and direct pulmonary administration (INS) was first determined to obtain their basal pharmacokinetic (PK) parameters. Then, the disposition of CPZEN-45 powders after passive inhalation using consecutive and sequential doses was evaluated. Plasma concentration versus time curves and PK parameters indicated that the absorption of CPZEN-45 after INS was faster than after SC administration (Ka = 12.94 ± 5.66 h-1 and 1.23 ± 0.55 h-1, respectively), had a longer half-life (2.06 ± 1.01 h versus 0.76 ± 0.22 h) and had higher bioavailability (67.78% and 47.73%, respectively). The plasma concentration versus time profiles and the lung tissue concentration at the end of the study period were not proportional to the dose size after one, two, and three consecutive passive inhalation doses. Three sequential passive inhalation doses maintained therapeutic concentration levels in plasma and lung tissue for a longer time than three consecutive doses (10 h vs. 3 h, respectively). Future studies to evaluate the efficacy of inhaled CPZEN-45 powders should employ sequential doses of the powder, with one nominal dose administered to animals three times per day.

17.
Int J Ophthalmol ; 16(12): 1942-1951, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38111935

RESUMEN

AIM: To investigate the effect of electroacupuncture (EA) on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lens-induced myopia (LIM). METHODS: Guinea pigs were randomly divided into normal control (NC) group, LIM group, LIM+SHAM acupoint (LIM+SHAM) group, and LIM+EA group. Animals in the NC group received no intervention, while those in other three groups were covered with -6.0 diopter (D) lenses on right eyes. Meanwhile, animals in the LIM+EA group received EA at Hegu (LI4) combined with Taiyang (EX-HN5) acupoints, while those in the LIM+SHAM group were treated at sham points. After treatments for 1, 2, and 4wk, morphological changes in ciliary muscles were observed with hematoxylin and eosin (H&E) staining and nick end labeling (TUNEL), and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. Additionally, the adenosine triphosphate (ATP) contents were also determined in ciliary muscles. RESULTS: Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group. The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups, whereas those in the LIM+EA group improved significantly. TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups, whereas reduced in the LIM+EA group. ATP contents showed a significant decrease in the LIM and LIM+SHAM groups, whereas increased after EA treatment. Compared with the NC group, the dynamin-related protein 1 (DRP1), Caspase3, and apoptotic protease activator 1 (APAF1) levels were significantly increased in the LIM group and decreased in the LIM+EA group. CONCLUSION: The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

18.
PeerJ ; 11: e16425, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025747

RESUMEN

Purpose: Bright light conditions are supposed to curb eye growth in animals with experimental myopia. Here we investigated the effects of temporal bright light at very low frequencies exposures on lens-induced myopia (LIM) progression. Methods: Myopia was induced by application of -6.00 D lenses over the right eye of guinea pigs. They were randomly divided into four groups based on exposure to different lighting conditions: constant low illumination (CLI; 300 lux), constant high illumination (CHI; 8,000 lux), very low frequency light (vLFL; 300/8,000 lux, 10 min/c), and low frequency light (LFL; 300/8,000 lux, 20 s/c). Refraction and ocular dimensions were measured per week. Changes in ocular dimensions and refractions were analyzed by paired t-tests, and differences among the groups were analyzed by one-way ANOVA. Results: Significant myopic shifts in refractive error were induced in lens-treated eyes compared with contralateral eyes in all groups after 3 weeks (all P < 0.05). Both CHI and LFL conditions exhibited a significantly less refractive shift of LIM eyes than CLI and vLFL conditions (P < 0.05). However, only LFL conditions showed significantly less overall myopic shift and axial elongation than CLI and vLFL conditions (both P < 0.05). The decrease in refractive error of both eyes correlated significantly with axial elongation in all groups (P < 0.001), except contralateral eyes in the CHI group (P = 0.231). LFL condition significantly slacked lens thickening in the contralateral eyes. Conclusions: Temporal bright light at low temporal frequency (0.05 Hz) appears to effectively inhibit LIM progression. Further research is needed to determine the safety and the potential mechanism of temporal bright light in myopic progression.


Asunto(s)
Iluminación , Miopía , Animales , Cobayas , Ojo , Miopía/prevención & control , Refracción Ocular , Errores de Refracción
19.
Parasite ; 30: 37, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37728509

RESUMEN

Enterocytozoon bieneusi, the most common microsporidian species, has been detected in humans and a variety of animals worldwide. However, limited information is available on the prevalence and molecular characterization of this parasite in guinea pigs. In this study, we conducted the first investigation of E. bieneusi infection in hairless guinea pigs recently introduced into China as new exotic pets. A total of 324 fecal samples were collected from hairless guinea pigs from a pet market and four breeding facilities in China. Sequence alignment of the internal transcribed spacer (ITS) revealed an infection rate of 14.2% (46/324) and two known ITS genotypes, S7 and PGP. Genotype S7 was the dominant genotype in these animals (42/46, 91.3%). Due to significant ITS sequence divergence, four and two PGP isolates from hairless and regular guinea pigs, respectively were further identified by PCR and phylogenetic analysis based on the small subunit (SSU) rRNA gene, as well as phylogenetic analysis of the ITS locus using E. hepatopenaei and two related genera Enterospora and Nucleospora as the outgroup. Three out of the six PGP isolates were successfully sequenced and generated the same sequences. Phylogenetic analysis of SSU rRNA and ITS loci revealed that PGP isolates formed a separate clade that was distinct and far away from E. bieneusi, suggesting that they represent a new species of Enterocytozoon. These findings indicate the dominance of zoonotic E. bieneusi genotype S7 in hairless guinea pigs and the existence of a cryptic Enterocytozoon species in guinea pigs.


Title: Prévalence et caractérisation moléculaire d'Enterocytozoon bieneusi et d'une nouvelle espèce d'Enterocytozoon chez des cobayes sans poils (Cavia porcellus) en Chine. Abstract: Enterocytozoon bieneusi, l'espèce de microsporidies la plus commune, a été détectée chez les humains et chez divers animaux à travers le monde. Cependant, peu d'informations sont disponibles sur la prévalence et la caractérisation moléculaire de ce parasite chez le cobaye. Dans cette étude, nous avons mené la première enquête sur l'infection par E. bieneusi chez des cobayes sans poils récemment introduits en Chine en tant que nouveaux animaux de compagnie exotiques. Trois cent vingt-quatre échantillons fécaux ont été collectés sur des cobayes sans poils provenant d'un marché d'animaux de compagnie et de quatre établissements d'élevage en Chine. L'alignement des séquences de l'espaceur transcrit interne (ITS) a révélé le taux d'infection (14,2 %, 46 / 324) et deux génotypes ITS connus (S7 et PGP). Le génotype S7 était le génotype dominant chez ces animaux (42 / 46, 91,3 %). En raison d'une divergence significative des séquences ITS, quatre et deux isolats de PGP provenant respectivement de cobayes sans poils et ordinaires ont été identifiés par PCR, analyse phylogénétique basée sur le gène de l'ARNr de la petite sous-unité (SSU), ainsi que par analyse phylogénétique du locus ITS en utilisant E. hepatopenaei et deux genres apparentés Enterospora et Nucleospora comme groupe externe. Trois des six isolats de PGP ont été séquencés avec succès et ont généré les mêmes séquences. L'analyse phylogénétique de l'ARNr SSU et des loci ITS a révélé que les isolats de PGP formaient un clade distinct et éloigné de E. bieneusi, ce qui suggère qu'ils représentent une nouvelle espèce d'Enterocytozoon. Ces résultats indiquent la domination du génotype zoonotique E. bieneusi S7 chez les cobayes sans poils et l'existence d'une espèce cryptique d'Enterocytozoon chez les cobayes.


Asunto(s)
Enterocytozoon , Humanos , Cobayas , Animales , Enterocytozoon/genética , Prevalencia , Filogenia , Fitomejoramiento , China/epidemiología
20.
Exp Eye Res ; 235: 109619, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37633324

RESUMEN

PURPOSE: To investigate the impact of different duration of blue light exposure on ocular parameters and choroidal blood perfusion in guinea pigs with lens-induced myopia. METHOD: Three-week-old Guinea pigs were randomly assigned to different light-environment groups. All groups were subjected to 12-h light/dark cycle. The control (NC) group was conditioned without intervention. While lens-induced myopia (LIM) groups had a -10D lens placed in the right eye and 0D in the left eye. The guinea pigs were exposed to increasing periods of blue-light (420 nm) environment for 3,6,9,12 h per day. Changes in refraction, axial length (AL), the radius of corneal curvature (CCR), choroidal thickness (ChT), and choroidal blood perfusion (ChBP)were measured in both LIM-eye and fellow-eye during the second and fourth week of LIM duration. RESULTS: During the first two weeks of the experiment, blue light exposure raised ChBP and ChT, and the effect of suppressing myopia was proportional to the duration of blue light exposure. However, in the fourth week of the experiment, prolonged blue light (12BL) exposure led to a reduction in retinal thickness and the increase in ChT and ChBP ceased. Shorter blue light exposure had a better effect on myopia suppression, with all blue light groups statistically different from the LIM group. CONCLUSION: Exposure to blue-light appears to have the potential to improve ChBP and ChT, thereby inhibiting the development of myopia. we speculate that blue-light inhibits the development of myopia for reasons other than longitudinal chromatic aberration (LCA). However,long-term exposure to blue-light may have adverse effects on ocular development. The next step is to investigate in depth the mechanisms by which the rational use of blue light regulates choroidal blood flow, offering new hope for the treatment of myopia.


Asunto(s)
Miopía , Animales , Cobayas , Coroides , Modelos Animales de Enfermedad , Luz , Miopía/etiología , Perfusión , Refracción Ocular
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