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International Journal of Infectious... Jun 2024Monkeypox (Mpox) is a neglected viral endemic tropical disease in both Central and Western African countries transmitted to humans by an animal. However, the natural...
Monkeypox (Mpox) is a neglected viral endemic tropical disease in both Central and Western African countries transmitted to humans by an animal. However, the natural reservoir of the virus remains elusive. In this study we looked for potential reservoirs of MPXV in Gabonese wildlife to prevent future outbreaks and enrich the literature with additional data on animal reservoirs. DNA was extracted from livers and spleens from 2549 animals (bats (859), bushmeats (356), rodents (1309), and shrews (25)) collected between 2012 and 2021. DNA was analyzed by real-time and conventional PCR targeting the 14 KD Protein and the rpo subunit RNA polymerase of orthopoxviruses. No MPXV DNA was detected despite the presence of potential host reservoirs like Critcetomys, Crocidura, Praomys, and Atherurus africanus. This absence could be due to: (i) the low number of animals collected for some species, (ii) the acute nature of Mpox infection, but also (iii) the lack of the potential reservoir Funisciurus anerythrus among collected animals, and (iv) the fact that the samplings are not included in the probable ecological niche of MPXV. Longitudinal studies including potential ecological niches of both F. anerythrus and MPXV in Gabon may be useful to get more information on MPXV circulation.
PubMed: 38878993
DOI: 10.1016/j.ijid.2024.107106 -
Biomedicine & Pharmacotherapy =... Jun 2024Amauroderma rugosum (AR) is a medicinal mushroom commonly used to treat inflammation, gastric disorders, epilepsy, and cancers due to its remarkable anti-inflammatory...
Protective effects of Amauroderma rugosum on dextran sulfate sodium-induced ulcerative colitis through the regulation of macrophage polarization and suppression of oxidative stress.
BACKGROUND
Amauroderma rugosum (AR) is a medicinal mushroom commonly used to treat inflammation, gastric disorders, epilepsy, and cancers due to its remarkable anti-inflammatory and anti-oxidative properties. This study was designed to evaluate the pharmacological effects of AR and its underlying mechanism of action against ulcerative colitis (UC) in vitro and in vivo.
METHODS
A UC mouse model was established by administration of dextran sulfate sodium (DSS). AR extract was administered intragastrically to mice for 7 days. At the end of the experiment, histopathology, macrophage phenotype, oxidative stress, and inflammatory status were examined in vivo. Furthermore, RAW 264.7, THP-1, and Caco-2 cells were used to elucidate the mechanism of action of AR in vitro.
RESULTS
AR extract (0.5-2 mg/mL) significantly suppressed lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced M1 macrophage (pro-inflammatory) polarization in both RAW 264.7 and THP-1 cells. LPS-induced pro-inflammatory mediators (nitric oxide, TNF-α, IL-1β, MCP-1, and IL-6) were reduced by AR extract in a concentration-dependent manner. Similarly, AR extract downregulated MAPK signaling activity in LPS-stimulated RAW 264.7 cells. AR extract elicited a concentration-dependent increase in the mRNA expression of M2 (anti-inflammatory) phenotype markers (CD206, Arg-1, Fizz-1, and Ym-1) in RAW 264.7 cells. Moreover, AR extract suppressed DSS-induced ROS generation and mitochondrial dysfunction in Caco-2 cells. The in vivo experiment revealed that AR extract (200 mg/kg) increased colon length compared to the DSS-treated group. In addition, disease activity index, spleen ratio, body weight, oxidative stress, and colonic inflammation were markedly improved by AR treatment in DSS-induced UC mice. Finally, AR suppressed M1 and promoted M2 macrophage polarization in UC mice.
CONCLUSION
The AR extract protected against DSS-induced UC by regulating macrophage polarization and suppressing oxidative stress. These valuable findings suggest that adequate intake of AR can prevent and/or treat UC.
PubMed: 38878683
DOI: 10.1016/j.biopha.2024.116901 -
Scientific Reports Jun 2024Antitumor drugs used today have shown significant efficacy and are derived from natural products such as plants. Iso-mukaadial acetate (IMA) has previously been shown to...
Antitumor drugs used today have shown significant efficacy and are derived from natural products such as plants. Iso-mukaadial acetate (IMA) has previously been shown to possess anticancer properties by inducing apoptosis. The purpose of this study was to investigate the therapeutic effect of IMA in the breast cancer xenograft mice model. Female athymic nude mice were used and inoculated with breast cancer cells subcutaneously. Untreated group one served as a negative control and positive control group two (cisplatin) was administered intravenously. IMA was administered orally to group three (100 mg/kg) and group four (300 mg/kg). Blood was collected (70 μL) from the tail vein on day zero, day one and day three. Tumor regression was measured every second day and body mass was recorded each day. Estimation of serum parameters for renal indices was examined using a creatinine assay. Histopathological analysis was conducted to evaluate morphological changes of liver, kidney, and spleen tissues before and after compound administration under a fluorescence light microscope. Histopathological analysis of tumors was conducted before and after compound administration. Apoptotic analysis using the TUNEL system was conducted on liver, kidney, and spleen tissues. Tumor shrinkage and reduction in body mass were observed after treatment with IMA. Serum creatinine was slightly elevated after treatment with IMA at a dosage of 100 and 300 mg/kg. Histopathological results of the liver exhibited no changes before and after IMA while the kidney and spleen tissues showed changes in the cellular structure. IMA showed no cytotoxic effect on the tumor cells, and cell proliferation was observed. Apoptotic assay stain with TUNEL showed apoptotic cells in spleen tissue and kidney but no apoptotic cells were observed in liver tissue section treated with IMA. IMA showed clinical toxic signs that resulted in the suffering and death of the mice immediately after IMA administration. Histopathology of tumor cells showed that IMA did not inhibit cell proliferation and no cellular damage was observed. Therefore, based on the results obtained, we cannot make any definitive conclusion on the complete effect of IMA in vivo. IMA is toxic, poorly soluble, and not safe to use in animal studies. The objective of the study was not achieved, and the hypothesis was rejected.
Topics: Animals; Humans; Female; Mice; Xenograft Model Antitumor Assays; Breast Neoplasms; Apoptosis; Mice, Nude; MCF-7 Cells; Antineoplastic Agents; Cell Proliferation
PubMed: 38877067
DOI: 10.1038/s41598-024-64474-x -
Scientific Data Jun 2024The Chungtien schizothoracin (Ptychobarbus chungtienensis), an endangered fish species endemic to the Zhongdian Plateau, remains underexplored in terms of transcriptomic...
The Chungtien schizothoracin (Ptychobarbus chungtienensis), an endangered fish species endemic to the Zhongdian Plateau, remains underexplored in terms of transcriptomic sequencing. This investigation used tissues from five distinct organs (heart, liver, spleen, kidney, and brain) of the Chungtien schizothoracin for PacBio Iso-seq and RNA-seq analyses, yielding a repertoire of 16,598 full-length transcripts spanning lengths from 363 bp to 7,157 bp. Gene family clustering and phylogenetic analysis encompassed a comprehensive set of 13 fish species, all of which were cyprinids, including the zebrafish and the examined species Ptychobarbus chungtienensis. Moreover, the identification of long non-coding RNAs (lncRNAs) and coding sequences was accomplished across all five tissues. Comprehensive analyses of gene expression profiles and differentially expressed genes among the above five tissues were performed. In summary, the obtained full-length transcripts and detailed gene expression profiles of the Chungtien schizothoracin tissues furnish crucial expression data and genetic sequences, laying the groundwork for future investigations and fostering a holistic comprehension of the adaptive mechanisms inherent in the Chungtien schizothoracin under various conditions.
Topics: Animals; Cyprinidae; Transcriptome; Phylogeny; RNA-Seq; RNA, Long Noncoding; Endangered Species
PubMed: 38877023
DOI: 10.1038/s41597-024-03491-x -
Nature Communications Jun 2024The capacity of HIV-1 to replicate during optimal antiretroviral therapy (ART) is challenging to assess directly. To gain greater sensitivity to detect evolution on ART,...
The capacity of HIV-1 to replicate during optimal antiretroviral therapy (ART) is challenging to assess directly. To gain greater sensitivity to detect evolution on ART, we used a nonhuman primate (NHP) model providing precise control over the level of pre-ART evolution and more comprehensive analyses than are possible with clinical samples. We infected 21 rhesus macaques (RMs) with the barcoded virus SIVmac239M and initiated ART early to minimize baseline genetic diversity. RMs were treated for 285-1200 days. We used several tests of molecular evolution to compare 1352 near-full-length (nFL) SIV DNA single genome sequences from PBMCs, lymph nodes, and spleen obtained near the time of ART initiation and those present after long-term ART, none of which showed significant changes to the SIV DNA population during ART in any animal. To investigate the possibility of ongoing replication in unsampled putative tissue sanctuaries during ART, we discontinued treatment in four animals and confirmed that none of the 336 nFL SIV RNA sequences obtained from rebound plasma viremia showed evidence of evolution. The rigorous nature of our analyses reinforced the emerging consensus of a lack of appreciable ongoing replication on effective ART and validates the relevance of this NHP model for cure studies.
Topics: Animals; Simian Immunodeficiency Virus; Simian Acquired Immunodeficiency Syndrome; Macaca mulatta; Virus Replication; Anti-Retroviral Agents; Evolution, Molecular; RNA, Viral; Viral Load; Viremia; DNA, Viral; Male
PubMed: 38877003
DOI: 10.1038/s41467-024-49369-9 -
International Journal of... 2024TYK2 inhibitors and traditional natural drugs as promising drugs for psoriasis therapy are receiving increasing attention. They both affect different molecules of...
INTRODUCTION
TYK2 inhibitors and traditional natural drugs as promising drugs for psoriasis therapy are receiving increasing attention. They both affect different molecules of JAK/STAT pathway, but it is currently unclear whether their combination will enhance the effect on psoriasis. In this study, we used imiquimod (IMQ)-induced psoriasis mouse model to investigate the therapeutic effects of the combined administration of deucravacitinib (TYK2 inhibitor) and shikonin.
METHODS
Aldara cream containing 5% IMQ was used to topically treat the dorsal skin of each mouse for a total of six consecutive days to induce psoriasis. The psoriasis area and severity index (PASI) scores were recorded every day. On the 7 day, skin tissues were taken for histopathological examination and the content of cytokines in skin were evaluated. The frequency of immune cells in peripheral blood, spleen and skin were detected through flow cytometry.
RESULTS
Compared to the vehicle control group, the psoriasis symptoms and immune disorder improved significantly in the combination therapy group and deucravacitinib treatment group on the 7th day, and the expressions of p-STAT3 and Ki67 in skin were reduced as well. Moreover, the combined treatment of deucravacitinib and shikonin for psoriasis was superior to the monotherapy group, especially in inhibiting abnormal capillaries proliferation, reducing immune cells infiltration and decreasing the concentration of IL-12p70 in skin.
CONCLUSION
The combination of deucravacitinib and shikonin is a promising clinical application.
Topics: Animals; Psoriasis; Imiquimod; Naphthoquinones; Drug Therapy, Combination; Mice; Skin; Disease Models, Animal; Cytokines; Mice, Inbred BALB C; Male; Female; Benzimidazoles; Quinolones
PubMed: 38876119
DOI: 10.1177/03946320241260262 -
Biomedicine & Pharmacotherapy =... Jun 2024The unresectable or postoperative recurrence of advanced metastatic colorectal cancer (CRC) is the difficulty of its clinical management, and pharmacological therapy is...
The unresectable or postoperative recurrence of advanced metastatic colorectal cancer (CRC) is the difficulty of its clinical management, and pharmacological therapy is the main source of benefit. Immune checkpoint inhibitors are therapeutic options but are effective in approximately 5 % of patients with deficient mismatch repair (MMR)/microsatellite instability CRC and are ineffective in patients with MMR-proficient (pMMR)/microsatellite stable (MSS) CRCs, which may be associated with the tumor microenvironment (TME). Here, we propose a new combination strategy and evaluate the efficacy of rapamycin (Rapa) combined with anti-PD-1 (αPD-1) in CT26 tumor-bearing mice, azoxymethane (AOM)/dextran sodium sulfate (DSS) inflammation-associated CRC mice, CT26-Luc tumor-bearing mice with postoperative recurrence, and CT26 liver metastasis mice. The results revealed that Rapa improved the therapeutic effect of αPD-1 and effectively inhibited colorectal carcinogenesis, postoperative recurrence, and liver metastasis. Mechanistically, Rapa improved the anticancer effect of αPD-1, associated with Rapa reprograming of the immunosuppressive TME. Rapa effectively depleted α-SMA cancer-associated fibroblasts and degraded collagen in the tumor tissue, increasing T lymphocyte infiltration into the tumor tissue. Rapa induced the downregulation of programed cell death 1 ligand 1 (PD-L1) protein and transcript levels in CT26 cells, which may be associated with the inhibition of the mTOR/P70S6K signaling axis. Furthermore, co-culture of tumor cells and CD8 T lymphocytes demonstrated that Rapa-induced PD-L1 downregulation in tumor cells increased spleen-derived CD8 T lymphocyte activation. Therefore, Rapa improves the anti-tumor effect of αPD-1 in CRCs, providing new ideas for its use to improve combinatorial strategies for anti-PD-1 immunotherapy.
PubMed: 38876047
DOI: 10.1016/j.biopha.2024.116883 -
Medicine Jun 2024Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor...
INTRODUCTION
Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor with unknown etiology, atypical clinical symptoms, nonspecific imaging manifestations, difficult disease diagnosis and poor prognosis.
CASE REPORT
This case report details a 42-year-old woman who was admitted to the hospital with a 1-year-old bilateral adrenal mass and 1-month-old left upper abdominal pain. Enhanced CT of the abdomen showed a right adrenal nodule and a large occupying lesion in the left adrenal region, with a high probability of pheochromocytoma. Intraoperatively, a huge tumor measuring about 12*12*10 cm was found in the left adrenal region, infiltrating the left kidney, spleen and pancreatic tail. Postoperative pathology: lymphocytes were found in the renal capsule and subcapsule, lymphocytes were found in the pancreas; lymphocytes were found in the spleen. Consider a tumor of the lymphohematopoietic system, possibly lymphoma.
CONCLUSION
This case demonstrates that primary adrenal diffuse large B-cell lymphoma (PADLBCL) is highly aggressive, has a poor prognosis, is prone to recurrence, has poor therapeutic outcomes, and is difficult to diagnose. Clinicians should consider the possibility of PADLBCL when encountering huge adrenal-occupying lesions and consider chemotherapy before surgery. Reducing the tumor size before surgery is a more favorable therapeutic approach, thus prolonging the patient life and improving the quality of survival.
Topics: Humans; Female; Lymphoma, Large B-Cell, Diffuse; Adrenal Gland Neoplasms; Adult; Tomography, X-Ray Computed; Adrenal Glands
PubMed: 38875421
DOI: 10.1097/MD.0000000000038298 -
Frontiers in Pharmacology 2024Ulcerative colitis (UC) is marked by recurring inflammation. Existing treatments are ineffective and may have toxic side effects. Thus, new therapeutic agents are...
INTRODUCTION
Ulcerative colitis (UC) is marked by recurring inflammation. Existing treatments are ineffective and may have toxic side effects. Thus, new therapeutic agents are urgently needed. We studied the botanical formula "Li-Hong Tang (LHT)", which contains two main ingredients, R. Br and (Hook. f. et Thoms.) H. Ohba. In this study, we aimed to identify the effects of LHT on UC and explore its potential mechanism.
METHODS
LHT was analyzed using a mass spectrometer (MS). DSS at a dose of 2.5% was utilized to develop UC in mice. The administered groups received low, medium, and high dosages (0.32 g/kg, 0.64 g/kg, and 1.28 g/kg) of LHT and the positive medication, sulfasalazine (0.2 g/kg), respectively. Body weight, disease activity index (DAI) score, colon length, spleen index, serum myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD) and inflammatory factor concentrations were monitored. The expression of NRF2 and HO-1 in colonic tissues was evaluated by immunohistochemistry. 16S rDNA sequencing was employed to investigate alterations in the gut microbiota of the mice, aiming to elucidate the extent of LHT's impact.
RESULTS
LHT may ameliorate DSS-induced colitis in mice by lowering inflammation, reducing oxidative stress, restoring the intestinal barrier, and influencing the NRF2/HO-1 pathway. Moreover, LHT treatment exhibited a regulatory effect on the gut microbiota, characterized by elevated levels of Patescibacteria, Verrucomicrobiota, , , and levels while decreasing and r levels. Further study indicated that MPO, NO, and inflammatory factors were positively correlated with , , , , and negatively with , , and Patescibacteria. Furthermore, colony network analysis revealed that was negatively associated with and , whereas was positively related to .
CONCLUSION
LHT protects against DSS-induced mice by inhibiting the inflammatory response, oxidative stress, and mucosal injury. The protective role may involve regulating the NRF2/HO-1 signaling pathway and gut microbiota.
PubMed: 38873425
DOI: 10.3389/fphar.2024.1413666 -
Veterinary and Animal Science Sep 2024This study investigated marula seed cake (MSC) as alternative protein source (APS) replacing soyabean meal (SBM) in indigenous chicken diets. Four hundred, 3-week-old...
This study investigated marula seed cake (MSC) as alternative protein source (APS) replacing soyabean meal (SBM) in indigenous chicken diets. Four hundred, 3-week-old Boschveld chicks were randomly allocated to 5 iso-energetic-nitrogenous maize and SBM-based grower diets with 0, 10, 15, 20, and 25 % MSC, each with 5 replicate pens of 16 birds, in a completely randomised design (CRD), for 9 weeks. Results showed that dietary MSC quadratically decreased bird overall feed intake (FI) ( < 0.001) and body weight gain (BWG) ( < 0.01) as it linearly decreased the weights of hot carcass (HCW; < 0.05), spleen ( < 0.05), jejunum ( < 0.05), ileum ( < 0.001), and caecum ( < 0.001). In contrast, MSC increased chicken serum glucose ( < 0.05), cholesterol ( = 0.001) and phosphate ( < 0.05) as it decreased its amylase activity ( < 0.01). Also, it decreased bird meat lightness at 45 min ( < 0.05) and its yellowness at 45 min ( < 0.001) and 24 h ( < 0.001) whilst it increased its redness at 45 min ( < 0.01) and 24 h ( < 0.05) post-slaughter. In addition, MSC decreased chicken bone medial diaphysis ( < 0.05) as it induced no effects ( > 0.05) on overall feed conversion efficiency (FCE) and all other parameters. In conclusion, feeding of ≤ 15 % dietary MSC is nutritionally safe for indigenous chickens whilst detrimental on bird appetite, growth and meat yield, however without significantly affecting their physiology, at higher inclusion levels.
PubMed: 38873090
DOI: 10.1016/j.vas.2024.100364