Advances in sarcopenia: mechanisms, therapeutic targets, and intervention strategies.

Sarcopenia is a multifactorial condition characterized by loss of muscle mass. It poses significant health risks in older adults worldwide. Both pharmacological and non-pharmacological approaches are reported to address this disease. Certain dietary patterns, such as adequate energy intake and essential amino acids, have shown positive outcomes in preserving muscle function. Various medications, including myostatin inhibitors, growth hormones, and activin type II receptor inhibitors, have been evaluated for their effectiveness in managing sarcopenia. However, it is important to consider the variable efficacy and potential side effects associated with these treatments. There are currently no drugs approved by the Food and Drug Administration for sarcopenia. The ongoing research aims to develop more effective strategies in the future. Our review of research on disease mechanisms and drug development will be a valuable contribution to future research endeavors.

Anti-Coronavirus Potential of Polyether Ionophores: The New Application of Veterinary Antibiotics in Livestock.

Coronaviruses have consistently posed a major global concern in the field of livestock industry and public health. However, there is currently a lack of efficient drugs with broad-spectrum antiviral activity to address the challenges presented by emerging mutated strains or drug resistance. Additionally, the method for identifying multitarget drugs is also insufficient. Aminopeptidase N (APN) and 3C-like proteinase (3CLpro) represent promising targets for host-directed and virus-directed strategies, respectively, in the development of effective drugs against various coronaviruses. In this study, maduramycin ammonium demonstrated a broad-spectrum antiviral effect by targeting both of the proteins. The binding domains 4 Å from the ligand of both target proteins shared a structural similarity, suggesting that screening and designing drugs based on these domains might exhibit broad-spectrum and highly effective antiviral activity. Furthermore, it was identified that the polyether ionophores' ability to carry zinc ion might be one of the reasons why they were able to target APN and exhibit antiviral effect. The findings of this experiment provide novel perspectives for future drug screening and design, while also offering valuable references for the utilization of polyether ionophores in the management of livestock health.

Design and synthesis of APN and 3CLpro dual-target inhibitors based on STSBPT with anticoronavirus activity.

Coronaviruses (CoVs) have continuously posed a threat to human and animal health. However, existing antiviral drugs are still insufficient in overcoming the challenges caused by multiple strains of CoVs. And methods for developing multi-target drugs are limited in terms of exploring drug targets with similar functions or structures. In this study, four rounds of structural design and modification on salinomycin were performed for novel antiviral compounds. It was based on the strategy of similar topological structure binding properties of protein targets (STSBPT), resulting in the high-efficient synthesis of the optimal compound M1, which could bind to aminopeptidase N and 3C-like protease from hosts and viruses, respectively, and exhibit a broad-spectrum antiviral effect against severe acute respiratory syndrome CoV 2 pseudovirus, porcine epidemic diarrhea virus, transmissible gastroenteritis virus, feline infectious peritonitis virus and mouse hepatitis virus. Furthermore, the drug-binding domains of these proteins were found to be structurally similar based on the STSBPT strategy. The compounds screened and designed based on this region were expected to have broad-spectrum and strong antiviral activities. The STSBPT strategy is expected to be a fundamental tool in accelerating the discovery of multiple targets with similar effects and drugs.

Unveiling the Potential of Nelumbo nucifera-Derived Liensinine to Target The Myostatin Protein and to Counteract Muscle Atrophy.

Muscle atrophy refers to a decline in muscle mass and function, which has become a global concern due to the aging population. Various clinical trials have investigated the inhibitors of myostatin (MSTN). They have shown promising improvements in muscle function and quality of life. However, there are no drugs specifically targeting MSTN that have been approved for clinical use. In this study, we virtually screened liensinine (LIE), a food (Nelumbo nucifera)-derived compound, with low toxicity, from over 1.1 million compounds. We subsequently identified it as a potential candidate that targets MSTN by a cellular thermal shift assay (CETSA) and drug affinity response target stability (DARTS) assay. Further validation through cellular and in vivo studies demonstrated its promising potential in combating muscle atrophy. The mechanism of action may involve hindering the interaction between MSTN and the activin receptor type IIB (ActRIIB) and downregulating the expression of downstream proteins, including the muscle RING-finger protein-1 (MuRF-1) and muscle atrophy F-box (MAFbx)/Atrogin-1, ultimately promoting muscle regeneration. These results provide a strong foundation for future studies to explore the therapeutic potential of LIE in clinical settings.

Oxidative stress, the blood-brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants.

In recent years, growing awareness of the role of oxidative stress in brain health has prompted antioxidants, especially dietary antioxidants, to receive growing attention as possible treatments strategies for patients with neurodegenerative diseases (NDs). The most widely studied dietary antioxidants include active substances such as vitamins, carotenoids, flavonoids and polyphenols. Dietary antioxidants are found in usually consumed foods such as fresh fruits, vegetables, nuts and oils and are gaining popularity due to recently growing awareness of their potential for preventive and protective agents against NDs, as well as their abundant natural sources, generally non-toxic nature, and ease of long-term consumption. This review article examines the role of oxidative stress in the development of NDs, explores the 'two-sidedness' of the blood-brain barrier (BBB) as a protective barrier to the nervous system and an impeding barrier to the use of antioxidants as drug medicinal products and/or dietary antioxidants supplements for prevention and therapy and reviews the BBB permeability of common dietary antioxidant suplements and their potential efficacy in the prevention and treatment of NDs. Finally, current challenges and future directions for the prevention and treatment of NDs using dietary antioxidants are discussed, and useful information on the prevention and treatment of NDs is provided.

Metarhizium anisopliae CQMa128 regulates antioxidant/detoxification enzymes and exerts acaricidal activity against Psoroptes ovis var. cuniculi in rabbits: A preliminary study.

The entomopathogenic fungi Metarhizium anisopliae is highly pathogenic toward arthropods. Here, we evaluated the efficacy of a commercial formulation of M. anisopliae against P. ovis var. cuniculi in vivo and in vitro and explored the acaricidal mechanism of M. anisopliae by determining the antioxidant/detoxification-related enzymes activities including glutathione S-transferase (GST), superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) in mites. The results showed that M. anisopliae had high acaricidal activity against P. ovis var. cuniculi in vitro, in a time- and dose-dependent manner, with 83.33 % mortality at day 9 and a median lethal time (LT50) of 6.10 days after applying 6.14 × 109 conidia/ml of M. anisopliae. In vivo experiments, M. anisopliae achieved 100 % therapeutic effect after 3 days, compared with only 62.21 % for ivermectin. Enzyme assays showed that M. anisopliae significantly upregulated activities of GST, SOD and CAT in Psoroptes mites. The results indicate that M. anisopliae may be an effective biological agent for control of P. ovis var. cuniculi infestations in rabbits and the acaricidal activity may be associated with the changes of enzyme activities of the detoxification and antioxidant system in Psoroptes mites.

High anti-Ascaris seroprevalence in fattening pigs in Sichuan, China, calls for improved management strategies.

BACKGROUND: Ascariasis, caused by Ascaris suum, is an important soil-transmitted parasitic disease of pigs worldwide. It leads to significant economic losses in the pork industry, as a consequence of low feed conversion efficiency in pigs and liver condemnation at slaughter. Despite ascariasis still being widespread on pig farms in many developing and the industrialised countries, there are surprisingly limited data on porcine ascariasis in China, where nearly half of the world's total pork is produced. METHODS: In the present study, using the recently developed A. suum-haemoglobin (As-Hb) antigen-based serological test, we screened 512 individual serum samples from fattening pigs from 13 farms across seven distinct locations of Sichuan Province in China for anti-Ascaris antibody. RESULTS: The prevalence of anti-Ascaris antibody ranged from 0% to 100% on the distinct farms, with the mean (overall) seroprevalence being > 60%. There was no significant difference in seroprevalence between the intensive and extensive farms. CONCLUSIONS: To our knowledge, this is the first study to measure anti-Ascaris seroprevalence in China. The results of this 'snapshot' investigation indicate that Ascaris infection in commercial pig farms in Sichuan Province is seriously underestimated, encouraging future, large-scale serological studies to assess the distribution and extent of Ascaris exposure and infection in various regions of China and the world.

Evaluation of an Indirect ELISA Using Recombinant Arginine Kinase for Serodiagnosis of Psoroptes ovis var. cuniculi Infestation in Rabbits.

Psoroptes ovis var. cuniculi is a common ectoparasite of the wild and domestic rabbits worldwide, which causes significant economic losses in commercial rabbit breeding. In China, the diagnosis of rabbits infested with P. ovis var. cuniculi currently relies on detection of clinical signs and Psoroptes mites in skin scrapings by microscopy examination. However, this method is not very efficient in detection of the low mite loads and/or sub-clinical infections. In the present study, we cloned and expressed an arginine kinase homolog gene from P. ovis var. cuniculi (Poc-AK) and used its recombinant protein rPoc-AK to develop an indirect enzyme-linked immunosorbent assay (iELISA) method for diagnosis of P. ovis var. cuniculi infestation in rabbits. The results showed that the rPoc-AK protein was ~61 kDa and had no signal peptide. The rPoc-AK-based iELISA achieved a 94.4% sensitivity and a 88.2% specificity, and was able to detect P. ovis var. cuniculi infection as early as the 1st week post-infection, prior to the appearance of clinical signs. Further field study showed 24.94% (66.33/266) clinically normal rabbits were seropositive with the highest and lowest seropositive rates for California (35.71%) and Belgian (15.14%), respectively. These results suggested that the rPoc-AK has potential as a diagnostic antigen for early P. ovis var. cuniculi infestation in rabbits.

Complete mitogenome of the dog cucumber tapeworm Dipylidium caninum (Cestoda, Dilepididae) from Southwest China.

The cucumber tapeworm Dipylidium caninum (Cestoda, Dilepididae) is a common intestinal parasite of dogs and cats and can cause dipylidiasis in humans, especially in infants and children. In this study, the complete mitogenome of this tapeworm was sequenced using next-generation sequencing technology. The entire genome was 14,226 bp in size and encoded 36 genes, including 12 protein-coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes. The phylogeny revealed that D. caninum grouped with other species from the order Cyclophyllidea and separated from species of Pseudophyllidea. Within the Dipylidiidae, both dog-originated D. caninum were phylogenetic distinctiveness from cat-originated D. caninum, suggesting that D. caninum may represent a species complex. Altogether, the complete mitogenome of D. caninum sequenced here should contribute to a better understanding of the phylogenetic and taxonomic placement of this species.

Characterization of the complete mitochondrial genome of Spirometra decipiens (Cestoda: Diphyllobothriidae) from China.

The plerocercoid larvae (spargana) of Spirometra decipiens (Cestoda: Diphyllobothriidae) can parasitize humans, causing the zoonotic sparganosis. In this study, the complete mitochondrial genome of this tapeworm was determined using an Illumina sequencing platform. The entire genome was 13,642 bp in length and contained 12 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and two non-coding regions. The phylogeny indicated that S. decipiens was closely related to Spirometra erinaceieuropaei and supported the monophyletic relationships between Spirometra, Diphyllobothrium, and Diplogonoporus within the Dipyllobothriidae. These results should contribute to a better understanding of the phylogenetic position of this species.

Sequencing and analysis of the complete mitochondrial genome of dog roundworm Toxocara canis (Nematoda: Toxocaridae) from USA.

The dog roundworm Toxocara canis (Nematoda: Toxocaridae) is an important zoonotic parasitic nematode and cause toxocariasis in human with a worldwide distribution. Herein, the complete mitochondrial genome of a representative of this nematode from USA was determined through next generation sequencing platform. The whole genome was 14,309 bp in size and encoded 12 protein-coding genes, 22 transfer RNAs, and 2 ribosomal RNAs. Phylogeny showed that although T. canis from USA and Australia were more closely related to each other than to that from Chinese, three T. canis isolates clustered together and formed paraphyletic relationships with T. cati and T. malayensis, supporting them as sister species among the family Toxocaridae. These cumulative mitochondrial DNA data should contribute to a better understanding of the phylogenetic relationship of this species.

The mitochondrial genome of the dog hookworm Ancylostoma caninum (Nematoda, Ancylostomatidae) from Southwest China.

The dog hookworm Ancylostoma caninum (Nematoda, Ancylostomatidae) is a blood-feeding intestinal parasitic nematode and can cause ancylostomiasis in humans. In this study, the complete mitochondrial genome of this anthropozoonotic hookworm was sequenced through Illumina deep sequencing technology. The whole genome was 13,721 bp in length and encoded 36 genes including 12 protein-coding genes, 22 transfer RNAs, and 2 ribosomal RNAs. Phylogeny revealed that A. caninum grouped with species from Ancylostomatinae and separated from species of Bunostominae in the family Ancylostomatidae. Amongst the subfamily Ancylostomatinae, three dog-originated A. caninum, regardless of isolate origins, clustered together and were more closely related to the cat hookworm A. tubaeforme and the human hookworm A. duodenale than to the dog/cat hookworm A. ceylanicum and the sea lion hookworm Uncinaria sanguinis. Taken together, the cumulative mitochondrial DNA data provides insights into phylogenetic studies among Ancylostomatidae nematodes.

Characterization of the complete mitochondrial genome sequence of the dog roundworm Toxascaris leonina (Nematoda, Ascarididae) from China.

Toxascaris leonina (Nematoda, Ascarididae) is a cosmopolitan nematode of canids and felids and poses potential threats to public health due to aberrant larva migrans. Herein, the complete mitochondrial genome sequence of a representative of this nematode from the dog in China was determined using next-generation sequencing technology. The assembled genome was 14,357 bp in length and encoded 36 genes, including 12 protein-coding genes, 22 transfer RNAs and 2 ribosomal RNAs. The phylogeny revealed that the canid-originated T. leonina were phylogenetic distinctiveness from the felid-originated T. leonina within the genus Toxascaris of Ascarididae, supporting that T. leonina may represent a species complex.

Parasites of the Giant Panda: A Risk Factor in the Conservation of a Species.

The giant panda, with an estimated population size of 2239 in the world (in 2015), is a global symbol of wildlife conservation that is threatened by habitat loss, poor reproduction and limited resistance to some infectious diseases. Of these factors, some diseases caused by parasites are considered as the foremost threat to its conservation. However, there is surprisingly little published information on the parasites of the giant panda, most of which has been disseminated in the Chinese literature. Herein, we review all peer-reviewed publications (in English or Chinese language) and governmental documents for information on parasites of the giant pandas, with an emphasis on the intestinal nematode Baylisascaris schroederi (McIntosh, 1939) as it dominates published literature. The purpose of this chapter is to: (i) review the parasites recorded in the giant panda and describe what is known about their biology; (ii) discuss key aspects of the pathogenesis, diagnosis, treatment and control of key parasites that are reported to cause clinical problems and (iii) conclude by making some suggestions for future research. This chapter shows that we are only just 'scratching the surface' when it comes to parasites and parasitological research of the giant panda. Clearly, there needs to be a concerted research effort to support the conservation of this iconic species.