Chirality-Dependent Reprogramming of Macrophages.

The chirality of materials directly influences their transport and biological effects in physiological conditions. However, the impact of chiral materials on cellular metabolic reprogramming remains incompletely elucidated. In this study, we have synthesized chiral gold particles through a light-driven particle growth approach and demonstrated that d-Au particles exhibited superior macrophage activation ability compared to l-Au particles. An inflammatory creatine-phosphocreatine shunt was induced following d-Au stimulation. This shunt, facilitated by the upregulated expression of creatine kinase muscle-type (CKM), also resulted in a reduction in cytosolic levels of creatine. Pharmacological inhibition and genetic ablation of CKM further suppressed the secretion of pro-inflammatory cytokines, without compromising mitochondrial respiration. Moreover, the activation of macrophages induced by d-Au was mediated through the activation of the NF-κB and NLRP3 inflammasome pathways. Inhibition of CKM expression not only decreased the secretion of CXCL2 but also attenuated IL-1ß by suppressing the NLRP3 inflammasome pathways. Our investigation into the metabolic reprogramming mechanism of chiral materials on macrophage activation is pivotal for the application of chiral-based anticancer therapies.

Assessing Individual Muscle Characteristics to Enhance Frozen-Thawed Meat Quality.

This study assessed previous research aimed at mitigating the adverse effects of freeze-thawing on meat quality. Specifically, it focuses on assessing the physicochemical alterations in meat resulting from freezing, freeze-thawing, or technologies to minimize these alterations. Recent studies have focused on conventional freeze-thaw technology applicable across various livestock species and muscle types. However, recent research has indicated the necessity for developing freeze-thaw technology considering the unique characteristics of individual muscles. In this review, we summarize previous studies that have compared alterations in the physicochemical properties of primary muscles owing to freezing or freeze-thawing. Despite the introduction of various technologies to significantly reduce the adverse effects on meat quality resulting from freeze-thawing, it is essential to consider the unique characteristics (proximate composition, pH, and muscle fiber characteristics) of individual muscles or cuts to develop enhanced the freeze-thaw processing technology.

Characterization and discrimination of lamb with different breeds and muscle types using precursors and volatile compounds.

The unique aromas of mutton stem from the chemical reactions between the characteristic precursors during cooking. This study aimed to establish the relationship of volatile compounds and aroma precursors (protein, fat, free amino acids and fatty acids) in lamb from different breeds and muscle types. Hong lamb was characterized by greater tenderness and water holding capacity, higher polyunsaturated fatty acids and higher essential/non-essential amino acids in comparison with Hu lamb. Aldehydes, such as heptanal, hexanal, octanal and nonanal were higher in Hong-ST compared with Hu-ST. Principal component analysis (PCA) showed that aroma precursors were closely related to volatile components of cooked lamb. Discriminant analysis results showed that precursors and volatile compounds could be used to identify the breeds and muscle types of lamb. These findings revealed the contributors of lamb aroma and might help understand the regulatory mechanism of aroma in lamb from different breeds and muscle types.

The fatty acid profile and the quality of breast and leg muscles in female and male pearl gray guinea fowl (Numida meleagris).

The aim of this study was to evaluate the fatty acid (FA) profile and the quality of breast and leg muscles in male and female guinea fowl. In comparison with leg muscles, breast muscles had a higher content of dry matter and total protein, and contained less fat and total collagen (P ≤ 0.05). Sex had no effect on the chemical composition of the studied muscles or the FA profile of intramuscular fat (IMF) (P > 0.05). The IMF of breast muscles was characterized by higher proportions of total saturated fatty acids (SFAs) and polyunsaturated fatty acids (PUFAs), and lower proportions of total unsaturated fatty acids (UFAs) and monounsaturated fatty acids (MUFAs) (P ≤ 0.05) than the IMF of leg muscles. The physicochemical properties of guinea fowl meat were significantly influenced by muscle type (P ≤ 0.05), but not by sex (P > 0.05). Leg muscles were characterized by a higher pH, higher cooking loss, lower lightness (L*), lower drip loss, a higher contribution of redness (a*), and a lower contribution of yellowness (b*) than breast muscles (P ≤ 0.05). The experimental factors had no effect on the sensory attributes or the shear force values of the analyzed muscles (P > 0.05). The unique sensory attributes, high protein content, and low fat content of the analyzed muscles indicate that guinea fowl meat can be a dietary supplement and an addition to other types of meat consumed, especially that most guinea fowl are reared in extensive farming systems that contribute to sustainable food production.

Glycogen phosphorylase isoenzyme GPbb versus GPmm regulation of ventromedial hypothalamic nucleus glucoregulatory neurotransmitter and counter-regulatory hormone profiles during hypoglycemia: Role of L-lactate and octadecaneuropeptide.

Glucose accesses the brain primarily via the astrocyte cell compartment, where it passes through the glycogen shunt before catabolism to the oxidizable fuel L-lactate. Glycogen phosphorylase (GP) isoenzymes GPbb and GPmm impose distinctive control of ventromedial hypothalamic nucleus (VMN) glucose-regulatory neurotransmission during hypoglycemia, but lactate and/or gliotransmitter involvement in those actions is unknown. Lactate or the octadecaneuropeptide receptor antagonist cyclo(1-8)[DLeu5] OP (LV-1075) did not affect gene product down-regulation caused by GPbb or GPmm siRNA, but suppressed non-targeted GP variant expression in a VMN region-specific manner. Hypoglycemic up-regulation of neuronal nitric oxide synthase was enhanced in rostral and caudal VMN by GPbb knockdown, yet attenuated by GPMM siRNA in the middle VMN; lactate or LV-1075 reversed these silencing effects. Hypoglycemic inhibition of glutamate decarboxylase65/67 was magnified by GPbb (middle and caudal VMN) or GPmm (middle VMN) knockdown, responses that were negated by lactate or LV-1075. GPbb or GPmm siRNA enlarged hypoglycemic VMN glycogen profiles in rostral and middle VMN. Lactate and LV-1075 elicited progressive rostral VMN glycogen augmentation in GPbb knockdown rats, but stepwise-diminution of rostral and middle VMN glycogen after GPmm silencing. GPbb, not GPmm, knockdown caused lactate or LV-1075 - reversible amplification of hypoglycemic hyperglucagonemia and hypercorticosteronemia. Results show that lactate and octadecaneuropeptide exert opposing control of GPbb protein in distinct VMN regions, while the latter stimulates GPmm. During hypoglycemia, GPbb and GPmm may respectively diminish (rostral, caudal VMN) or enhance (middle VMN) nitrergic transmission and each oppose GABAergic signaling (middle VMN) by lactate- and octadecaneuropeptide-dependent mechanisms.

An insight into farm animal skeletal muscle metabolism based on a metabolomics approach.

Farm animal skeletal muscle, formed through development, growth, and maturation processes, is converted to edible meat during postmortem rigor mortis and aging. Live and postmortem muscle metabolism is the phenotypic determinant of muscle characteristics and meat quality traits such as flavor and color. Meanwhile, animal muscle metabolism, originally programmed by genetic program, is modulated by feeding and environmental conditions through changes in the biosynthetic network. Metabolomics deepens our understanding of metabolisms underlying skeletal muscle growth, maturation, abnormality, and postmortem meat aging. The metabolomics approach is beneficial to explore biomarkers to monitor meat production processes and products, leading to improvements in livestock productivity and meat quality. One of the recent metabolomics findings in animal muscle could be the impact of mitochondrial activity and energy metabolisms on meat quality. The present review overviews the advances in metabolomics studies of farm animal skeletal muscle, to gain an insight into the muscle metabolisms associated with livestock production and meat quality.

New Insight into Muscle-Type Cofilin (CFL2) as an Essential Mediator in Promoting Myogenic Differentiation in Cattle.

Meat quality and meat composition are not separated from the influences of animal genetic improvement systems; the growth and development of skeletal muscle are the primary factors in agricultural meat production and meat quality. Though the muscle-type cofilin (CFL2) gene has a crucial influence on skeletal muscle fibers and other related functions, the epigenetic modification mechanism of the CFL2 gene regulating meat quality remains elusive. After exploring the spatiotemporal expression data of CFL2 gene in a group of samples from fetal bovine, calf, and adult cattle, we found that the level of CFL2 gene in muscle tissues increased obviously with cattle age, whereas DNA methylation levels of CFL2 gene in muscle tissues decreased significantly along with cattle age by BSP and COBRA, although DNA methylation levels and mRNA expression levels basically showed an opposite trend. In cell experiments, we found that bta-miR-183 could suppress primary bovine myoblast differentiation by negatively regulated CFL2. In addition, we packaged recombinant adenovirus vectors for CFL2 gene knockout and overexpression and found that the CFL2 gene could promote the differentiation of primary bovine myoblasts by regulating marker genes MYOD, MYOG and MYH3. Therefore, CFL2 is an essential mediator for promoting myogenic differentiation by regulating myogenic marker genes in cattle myoblasts.

Fatty acid and conjugated linoleic acid content of Anatolian buffaloes at different muscle types and slaughter weight.

This research was performed to detect tissue fatty acid (FA) composition and conjugated linoleic acid (CLA) content in Anatolian buffaloes at different muscle types (MTs) and slaughter weights (SWs). The research was carried out on a private commercial livestock farm in Tokat. The research's animal material comprised 20 Anatolian buffalo calves with approximately 100 kg body weights, weaned at about 150 days of age. Before the experiment started, the calves were randomly divided into two slaughter groups (SW) as low weight (LW=225 kg) and high weight (HW=325 kg). Ten calves from each of the two experimental groups, which were intensively fed, were slaughtered in two different weights. After the slaughtering, FA composition and CLA content of the Semimembranosus (SM), Semitendinosus (ST), and Triceps brachii (TB) muscle tissues of the animals were examined. The study determined that palmitoleic acid (C16:1) and stearic acid (C18:0) were affected by MTs and oleic acid (C18:1) and α-linolenic acid (C18:3 n-3) were affected by SW (P < 0.05). The highest CLA was in the ST muscle type (0.298) and the LW group (0.289) of the SW groups (P > 0.05). With the increase of SW (in LW and HW groups), n-6/n3 (SM: 7.783 and 6.533; ST: 8.115 and 7.859; TB: 8.416 and 8.215) (P > 0.05) and PUFA ratio decreased (P < 0.05). The SW increase raised the SFA ratio in the SM muscle (P < 0.05) while lowering it in the TB muscle (P > 0.05). Again, with the increase in SW, AI and TI values increased in SM and ST muscles, while the same index values decreased in TB muscle (P > 0.05). In conclusion, when considering the PUFA/SFA ratio and the beneficial effects of CLAs on human health, ST in the MT and LW groups in SW, and thus ST and LW in MT and SW were prominent in Anatolian buffaloes.

Receptor subunit compositions underly distinct potencies of a muscle relaxant in fast and slow muscle fibers.

A line of studies in the 1960s-1980s suggested that muscle relaxants do not work uniformly on all skeletal muscles, though its mechanism has not been clarified. We showed here that a classical non-depolarizing muscle relaxant pancuronium inhibits fast muscle fibers at lower concentration compared to slow muscle fibers in zebrafish. The difference of effective concentration was observed in locomotion caused by tactile stimulation as well as in synaptic currents of the neuromuscular junction induced by motor neuron excitation. We further showed that this difference arises from the different composition of acetylcholine receptors between slow and fast muscle fibers in the neuromuscular junction of zebrafish. It will be interesting to examine the difference of subunit composition and sensitivity to muscle relaxants in other species.

Analysis of meat color, meat tenderness and fatty acid composition of meat in second filial hybrid offspring of MSTN mutant pigs.

The objective of this study was to assess the meat quality in second filial hybrid offspring of MSTN-/- cloning boars × Chinese Bama sows with initial mean body weight of 90.52 ± 0.68 kg. Compared with wild-type pigs, the feed utilization rate of MSTN-/- pigs showed an increasing trend (adjusted P = 0.06), loin eye area of MSTN-/- and MSTN+/- pigs increased (adjusted P < 0.01) and thickness of subcutaneous fat decreased (adjusted P < 0.01), the proportion of polyunsaturated fatty acids in meat of MSTN-/- pigs increased (adjusted P < 0.05). By means of histochemical staining, immunofluorescence, scanning electron microscopy, qRT-PCR and WB technologies, it was verified that the decreased meat color score of MSTN-/- pigs was related to the increase of type IIB muscle fiber, and the increased pork tenderness was related to the decrease of collagen content. Overall, this research provides reference for the further utilization of MSTN gene mutant pigs.

Effect of sampling position in fresh, dry-aged and wet-aged beef from M. Longissimus dorsi of Simmental cattle analyzed by 1H NMR spectroscopy.

The aging of beef affects the metabolome and, thus, its quality, such as taste or tenderness. In addition to the aging method, intrinsic factors, such as breed, feed and muscle type, also have an effect on beef's metabolome. It is not known yet whether the position of the sampling in large muscles also has an influence on beef's metabolome and its aging outcome. The effect of the sampling position in M. longissimus dorsi as a large muscle was investigated in dry-aged and wet-aged beef over an aging period of 28 days. In this study, we analyzed 360 samples out of the entire length of M. longissimus dorsi of 18 'Simmental' young bulls by 1H NMR spectroscopy. The position in the muscle affected the polar fraction of metabolome of non-aged and aged beef significantly. However, sampling position did not overlay significant differences in the metabolome of dry-aged and wet-aged beef. The aging time of beef also had a significant effect on the metabolome. Marker metabolites, such as leucine, isoleucine, inosine 5'-monophosphate and hypoxanthine, were found to be indicative of the aging time applied. In addition, marker metabolites (lactic acid, anserine, O-acetyl-L-carnitine) were identified for the aging type applied.

Effects of Age and Muscle Type on the Chemical Composition and Quality Characteristics of Bactrian Camel (Camelus bactrianus) Meat.

Camel meat could have health benefits for human consumers due to its nutritional value. The influence of age and muscle type on the chemical composition and quality characteristics of Bactrian camel meat was examined in the present study. Samples of the Longissimus thoracic (LT), Semitendinosus (ST), and Psoas major (PM) muscles were collected from a total of fifteen male camels in three different age groups (3−4 years, 6−7 years, and 9−10 years). The younger camels exhibited higher values of moisture, polyunsaturated fatty acids, ultimate pH, cooking loss, and lightness, but lower fat, shear force, and redness values compared to meat collected from older camels. The LT muscle had higher fat and color parameters (lightness, redness, yellowness) but lower shear force values than the ST and PM muscles (p < 0.05). The ST muscles had a higher content of n-6 polyunsaturated fatty acids and n-3 polyunsaturated fatty acids but lower cooking loss values than the LT and PM muscles. These results indicated that younger camels provide better meat quality traits than older camels. The results of the present study will improve the marketing of Bactrian camel meat products and will provide more information about the most suitable muscles and the optimal slaughter age.

Specific blockade of muscle acetylcholine receptor by α-conotoxin MIA and MIB / 药学学报

The α-conotoxins are peptide toxins that are identified from the venom of marine cone snails and they hold outstanding potency on various subtypes of nicotinic acetylcholine receptors (nAChRs). nAChRs have an important role in regulating transmitter release, cell excitability, and neuronal integration, so nAChR dysfunctions have been involved in a variety of severe pathologies. Four types of α-3/5 conotoxins MI, MIA, MIB and MIC have been found from Conus magus. Among them, the activity and selectivity of MIA and MIB have not been well studied. In this study, four α-3/5 conotoxins MI, MIA, MIB and MIC were synthesized by solid peptide synthesis method, and the bioactivities of them were screened by double electrode voltage clamp electrophysiology. The results showed that MIA and MIB selectively inhibited muscle type acetylcholine receptors with IC50 values of 14.45 and 72.78 nmol·L-1, respectively, which are slightly weaker than MI and MIC. Molecular docking results have shown MIA and MIB interact with muscle-type nAChRs with similar mechanism. The reasons for activity differences may relate to the size of the N-terminal amino acids. Together, the conotoxins MIA and MIB may have the potential to develop as a tool for detect the function of muscle type nAChRs, as well as the diagnosis or treat of related diseases.

Glycogen Phosphorylase Isoform Regulation of Ventromedial Hypothalamic Nucleus Gluco-Regulatory Neuron 5'-AMP-Activated Protein Kinase and Transmitter Marker Protein Expression.

Brain glycogen is remodeled during metabolic homeostasis and provides oxidizable L-lactate equivalents. Brain glycogen phosphorylase (GP)-brain (GPbb; AMP-sensitive) and -muscle (GPmm; norepinephrine-sensitive) type isoforms facilitate stimulus-specific control of glycogen disassembly. Here, a whole animal model involving stereotactic-targeted delivery of GPmm or GPbb siRNA to the ventromedial hypothalamic nucleus (VMN) was used to investigate the premise that these variants impose differential control of gluco-regulatory transmission. Intra-VMN GPmm or GPbb siRNA administration inhibited glutamate decarboxylate65/67 (GAD), a protein marker for the gluco-inhibitory transmitter γ--aminobutyric acid (GABA), in the caudal VMN. GPbb knockdown, respectively overturned or exacerbated hypoglycemia-associated GAD suppression in rostral and caudal VMN. GPmm siRNA caused a segment-specific reversal of hypoglycemic augmentation of the gluco-stimulatory transmitter indicator, neuronal nitric oxide synthase (nNOS). In both cell types, GP siRNA down-regulated 5'-AMP-activated protein kinase (AMPK) during euglycemia, but hypoglycemic suppression of AMPK was reversed by GPmm targeting. GP knockdown elevated baseline GABA neuron phosphoAMPK (pAMKP) content, and amplified hypoglycemic augmentation of pAMPK expression in each neuron type. GPbb knockdown increased corticosterone secretion in eu- and hypoglycemic rats. Outcomes validate efficacy of GP siRNA delivery for manipulation of glycogen breakdown in discrete brain structures in vivo, and document VMN GPbb control of local GPmm expression. Results document GPmm and/or -bb regulation of GABAergic and nitrergic transmission in discrete rostro-caudal VMN segments. Contrary effects of glycogenolysis on metabolic-sensory AMPK protein during eu- versus hypoglycemia may reflect energy state-specific astrocyte signaling. Amplifying effects of GPbb knockdown on hypoglycemic stimulation of pAMPK infer that glycogen mobilization by GPbb limits neuronal energy instability during hypoglycemia.

Calmodulin complexes with brain and muscle creatine kinase peptides.

Calmodulin (CaM) is a ubiquitous Ca2+ sensing protein that binds to and modulates numerous target proteins and enzymes during cellular signaling processes. A large number of CaM-target complexes have been identified and structurally characterized, revealing a wide diversity of CaM-binding modes. A newly identified target is creatine kinase (CK), a central enzyme in cellular energy homeostasis. This study reports two high-resolution X-ray structures, determined to 1.24 â€‹Å and 1.43 â€‹Å resolution, of calmodulin in complex with peptides from human brain and muscle CK, respectively. Both complexes adopt a rare extended binding mode with an observed stoichiometry of 1:2 CaM:peptide, confirmed by isothermal titration calorimetry, suggesting that each CaM domain independently binds one CK peptide in a Ca2+-depended manner. While the overall binding mode is similar between the structures with muscle or brain-type CK peptides, the most significant difference is the opposite binding orientation of the peptides in the N-terminal domain. This may extrapolate into distinct binding modes and regulation of the full-length CK isoforms. The structural insights gained in this study strengthen the link between cellular energy homeostasis and Ca2+-mediated cell signaling and may shed light on ways by which cells can 'fine tune' their energy levels to match the spatial and temporal demands.

Differences in phosphatidylcholine profiles and identification of characteristic phosphatidylcholine molecules in meat animal species and meat cut locations.

Phosphatidylcholine (PC) is an essential component of the plasma membrane. Its profile varies with species and tissues. However, the PC profiles in meat have not been explored in depth. This study aimed to investigate the differences in PC profiles between various meat animal species and meat cut sites, along with the identification of characteristic PC molecules. The results demonstrated that the PC profiles of chicken meat differed from those of other species. Significant differences were also observed between the PC profiles of pork meat and the meat obtained from other species. The amount of PCs containing ether bonds was high in pork meat. PCs containing an odd number of carbon atoms were characteristic of beef and lamb meats. Furthermore, PC profiles differed based on the muscle location in chicken and pork. These results suggest that the PC profiles of skeletal muscles are indicators of animal species and muscle location.

Tissue and gender-related differences in the elemental composition of juvenile ocean sunfish (Mola spp.).

Trace elements are potentially critical contaminants of aquatic environments and fish, occupying upper trophic levels, are especially vulnerable to bioaccumulation. Due to public health concerns, however, data on the elemental composition of non-commercially important marine species are particularly lacking. Ocean sunfish (Mola spp.) attain a low commercial value worldwide and information on their elemental composition is limited. In this context, we examined the concentration of 11 trace elements (V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Cd and Pb) in eight tissues [brain, gills, gelatin (subcutaneous white gelatinous layer), gonads, spleen, liver, white muscle and red muscle] of 20 juvenile specimens (37.5-85.5 cm TL). Gender-related differences were solely found in the gonads and chiefly for essential elements possibly as a result of their importance in embryo development. Overall, Zn and As were the elements observed in greatest concentrations in body tissues. The considerably high presence of As should be related to the dietary preferences of juvenile ocean sunfish. Considerable inter-individual variability in the concentration of each element in any given tissue was observed, especially in the liver, likely originating from the inclusion of both benthic and pelagic prey in the diet of analysed fish. Greatest elemental loads were found in the liver and gills whereas lowest loads were observed in white muscle, brain and gelatin. Moreover, a clear distinction in elemental load and elemental composition was observed between white and red muscles, likely deriving from existing divergent metabolism-related physiological adaptations linked to their different roles in locomotion.

Puerarin ameliorates skeletal muscle wasting and fiber type transformation in STZ-induced type 1 diabetic rats.

Puerarin is an isoflavonoid extracted from Pueraria lobate with extensive pharmacological effects in traditional Chinese medicine. The evidence implicates that puerarin mitigates hyperglycemia and various relevant complications. Here, the effect of puerarin on skeletal muscle wasting induced by type 1 diabetes (T1D) was explored. Streptozotocin (STZ)-induced T1D male Sprague Dawley (SD) rats were used in this study. Muscle strength, weight and size were measured. L6 rat skeletal muscle cells were applied for in vitro study. Our results showed that eight-week oral puerarin administration (100 mg/kg) increased muscle strengths and weights accompanied by enhanced skeletal muscle cross-sectional areas in diabetic rats. Simultaneously, puerarin also reduced expressions of several muscle wasting marker genes including F-box only protein 32 (Atrogin-1) and muscle-specific RING-finger 1 (Murf-1) in diabetic group both in vitro and in vivo. Transformation from type I fibers (slow muscle) to type II fibers (fast muscle) were also observed under puerarin administration in diabetic rats. Puerarin promoted Akt/mTOR while inhibited LC3/p62 signaling pathway in skeletal muscle cells. In conclusion, our study showed that puerarin mitigated skeletal muscle wasting in T1D rats and closely related with Akt/mTOR activation and autophagy inhibition. Whether this effect in murine applies to humans remains to be determined.

Mapping metal (Hg, As, Se), lipid and protein levels within fish muscular system in two fish species (Striped Bass and Northern Pike).

Current guidelines tend to limit fish consumption based on mercury (Hg) or monomethylmercury (MeHg) content in fish flesh, without considering the presence of antagonist chemical elements that could modulate Hg toxicity. However, it is difficult to assess the potential for antagonistic interactions of these elements since their covariation within muscle tissues is poorly known. Here we present the first study simultaneously mapping multiple metal(oid)s (Hg, As and Se), lipids and proteins in fish fillets in order to assess the magnitude of intra-organ variability of metals and the potential for antagonistic interactions. We mapped two fish species (Striped Bass and Northern Pike) with contrasting muscular structure with respect to the presence of white, intermediate and red muscles. In individual Striped Bass muscle tissues, metals varied on average by 2.2-fold. Methylmercury and selenium covaried strongly and were related to protein content as assessed by % N; arsenic was inversely related to these elements and was associated with the lipid fraction of the muscle. In Pike, no such relationship was found because the contents in proteins and lipids were less variable. Arsenic speciation revealed that arsenobetaine and arsenolipids were the only As species in those fish species, whereas the toxic inorganic As species (As3+) was under the detection limit. Arsenobetaine was related to % N, whereas arsenolipids covaried with % lipids. Elemental associations found with muscle lipids and proteins could help explain changes in bioaccumulation patterns within and between individuals with potential implications on fish toxicology, biomonitoring and human consumption guidelines.