Gastric cancer patient-derived organoids model for the therapeutic drug screening.

BACKGROUND: Gastric cancer (GC) is a highly heterogeneous disease featuring many various histological and molecular subtypes. Therefore, it is imperative to have well-characterized in vitro models for personalized treatment development. Gastric cancer patient-derived organoids (PDOs), re-capitulating in vivo conditions, exhibit high clinical efficacy in predicting drug sensitivity to facilitate the development of cancer precision medicine. METHODS: PDOs were established from surgically resected GC tumor tissues. Histological and molecular characterization of PDOs and primary tissues were performed via IHC and sequencing analysis. We also conducted drug sensitivity tests using PDO cultures with five chemotherapeutic drugs and twenty-two targeted drugs. RESULTS: We have successfully constructed a PDOs biobank that included EBV+, intestinal/CIN, diffuse/GS, mixed and Her2+ GC subtypes, and these PDOs captured the pathological and genetic characteristics of corresponding tumors and exhibited different sensitivities to the tested agents. In a clinical case study, we performed an additional drug sensitivity test for a patient who reached an advanced progressive stage after surgery. We discovered that the combination of napabucasin and COTI-2 exhibited a stronger synergistic effect than either drug alone. CONCLUSION: PDOs maintained the histological and genetic characteristics of original cancer tissues. PDOs biobank opens up new perspectives for studying cancer cell biology and personalized medicine as a preclinical study platform.

Characterization of Cinnamomum kanehirae Extract-Stimulated Triterpenoids Synthesis in Submerged Fermentation of Antrodia camphorata via Untargeted Metabolomics.

The underlying mechanisms of Cinnamomum kanehirae-stimulated growth and metabolism of Antrodia camphorata remain unknown. Herein, we first observed that the methanol extract of C. kanehirae trunk (MECK) (2 g/L) showed a potent stimulatory effect on A. camphorata triterpenoids production (115.6 mg/L). Second, MECK treatment considerably increased the category and abundance of many secondary metabolites in the mycelia. We identified 93 terpenoids (8 newly formed and 49 upregulated) in the MECK-treated mycelia, wherein 21 terpenoids were the same as those in the fruiting bodies. Third, 42 out of the 93 terpenoids were annotated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, mainly involving monoterpenoids and diterpenoids syntheses. Finally, 27 monoterpenes and 16 sesquiterpenes were detected in the MECK, and the two terpenoids with the highest abundance (linalool and α-pinene) were selected for verification and found to considerably increase the terpenoids production of A. camphorata and demonstrate the regulation of mRNA expression levels of nine key genes in the mevalonate pathway via RT-qPCR. This study is beneficial for elucidating the terpenoids synthesis mechanism in A. camphorata.

Magnesium Isoglycyrrhizinate Attenuates Anti-Tuberculosis Drug-Induced Liver Injury by Enhancing Intestinal Barrier Function and Inhibiting the LPS/TLRs/NF-κB Signaling Pathway in Mice.

Liver injury caused by first-line anti-tuberculosis (anti-TB) drugs accounts for a high proportion of drug-induced liver injury (DILI), and gut microbiota and intestinal barrier integrity have been shown to be involved in the development of DILI. Magnesium isoglycyrrhizinate (MgIG) is the fourth-generation glycyrrhizic acid preparation, which is well documented to be effective against anti-TB DILI, but the underlying mechanism is largely unclear. In the present study, we established a BALB/c mice animal model of the HRZE regimen (39 mg/kg isoniazid (H), 77 mg/kg rifampicin (R), 195 mg/kg pyrazinamide (Z), and 156 mg/kg ethambutol (E))-induced liver injury to investigate the protective effect of MgIG against anti-TB DILI and underlying mechanisms. The results demonstrated that intraperitoneal injection of MgIG (40 mg/kg) significantly ameliorated HRZE-induced liver injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and malondialdehyde (MDA) levels and improved liver pathological changes. Species composition analysis of gut microbiota showed that Lactobacillus was the only probiotic that was down-regulated by HRZE and recovered by MgIG. In addition, MgIG attenuated HRZE-induced intestinal pathology, significantly decreased HRZE-induced intestinal permeability by increasing the protein expression of tight junction protein 1 (ZO-1) and occludin, decreased HRZE-induced high lipopolysaccharide (LPS) levels, and further markedly attenuated mRNA expression levels of TNF-α, IL-6, TLR2, TLR4, and NF-κB. Supplementation with Lactobacillus rhamnosus JYLR-005 (>109 CFU/day/mouse) alleviated HRZE-induced liver injury and inflammation in mice. In summary, MgIG effectively ameliorated HRZE-induced liver injury by restoring the abundance of Lactobacillus, enhancing intestinal barrier function, and further inhibiting the activation of the LPS/TLRs/NF-κB signaling pathway. Regulating gut microbiota and promoting the integrity of intestinal barrier function may become a new direction for the prevention and treatment of anti-TB DILI.

Comparative effectiveness of glycyrrhizic acid preparations aimed at preventing and treating anti-tuberculosis drug-induced liver injury: A network meta-analysis of 97 randomized controlled trials.

BACKGROUND AND OBJECTIVES: Clinical guidelines and expert consensus do not yet recommend glycyrrhizic acid (GA) preparations, such as compound glycyrrhizin, diammonium glycyrrhizin, magnesium isoglycyrrhizinate (MGIG), et al., for the prevention of anti-tuberculosis(anti-TB) drug-induced liver injury (DILI) due to insufficient evidence. Although these GA preparations are recommended for the treatment of anti-TB DILI, which one performs best is unclear. Previous conventional meta-analyses did not summarize the results of simultaneous comparisons of different glycyrrhizinate preparations. Therefore, we aimed to compare and rank different GA preparations on preventing and treating the anti-TB DILI by network meta-analysis (NMA). METHODS: A systematic search on PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure, SinoMed, Chongqing VIP and, the Wanfang Database was performed up to December 19, 2020. The literature was screened according to predefined inclusion and exclusion criteria to extract important information. The outcomes were the incidence of liver injury (prevention section) and treatment response rate (treatment section). The NMA was conducted with a random-effects model under the Bayesian framework to calculate risk ratios (RRs) with 95% credible intervals (95% CrIs) using R software (version 3.6.1). RESULTS: From 1,411 publications, we included 97 relevant randomized clinical trials (RCTs) (10,923 participants). In terms of preventing anti-TB DILI (33 RCTs, comprising 5,762 patients), CGC, DGC, DGEC, and DGI, but not CGI, significantly reduced the incidence of liver injury than control group (RRs ranged from 0.26 to 0.58); CGC and DGEC were superior to DGC (RRs = 0.50 and 0.58, respectively). In terms of treating anti-TB DILI (64 RCTs, comprising 5,161 patients), MGIG was most effective among all regimens (RRs ranged from 1.15 to 1.72) while DGC ranked last (RRs ranged from 0.58 to 0.83). CONCLUSIONS: All GA preparations except for CGI were effective in preventing the incidence of anti-TB DILI and CGC was superior to DGC. MGIG seems to be the best choice among all GA preparations for the treatment of anti-TB DILI. Future clinical practice guidelines should factor in these novel findings to improve patient outcomes; however, further high-quality trials are needed to validate these results.

Effect of "Natural Polypill", Xuezhikang on Serum Cholesterol Metabolism Markers in Early Menopausal Women with Hypercholesterolemia / 中国结合医学杂志

OBJECTIVE@#To analyze the effect of Xuezhikang on the markers of the serum lipid levels of cholesterol synthesis and absorption in early menopausal women with hypercholesterolemia, and preliminarily explore its lipid-lowering mechanism.@*METHODS@#A total of 90 early menopausal women with hypercholesterolemia were enrolled from December, 2014 to May, 2016 from Beijing Anzhen Hospital, Capital Medical University, who were randomly allocated to receive Xuezhikang (1200 mg/d, orally) or atorvastatin (10 mg/d, orally) according to a random number table. Serum levels of some related biomarkers, including cholesterol synthesis markers (squalene, dihydrocholesterol, dehydrocholesterol, and lathosterol), and absorption markers (campesterol, stigmasterol, and sitosterol) as well as safety indices were obtained at baseline and after 8 weeks of the intervention.@*RESULTS@#Eight weeks after treatment, both Xuezhikang and atorvastatin significantly reduced the levels of total cholesterol, triglycerides, low density cholesterol compared to baseline (all P<0.01). Xuezhikang significantly reduced the levels of squalene, dehydrocholesterol and lathosterol compared to baseline (all P<0.01), but atorvastatin only significantly reduced the level of squalene (P<0.01), compared to baseline. All cholesterol absorption markers showed no significant differences before and after treatment (P>0.05), however, a more obvious downward trend was shown in the Xuezhikang group. In addition, all the safety indices showed no significant differences between the two groups. Although the creatinekinase level in the Xuezhikang group was significantly higher, it remained within the safe range.@*CONCLUSIONS@#Xuezhikang may have more comprehensive effects on the markers of cholesterol synthesis and metabolism in early menopausal women with hypercholesterolemia through ergosterol and flavonoids in its "natural polypill."

Phospholipids (PLs) know-how: exploring and exploiting phospholipase D for its industrial dissemination.

Owing to their numerous nutritional and bioactive functions, phospholipids (PLs), which are major components of biological membranes in all living organisms, have been widely applied as nutraceuticals, food supplements, and cosmetic ingredients. To date, PLs are extracted solely from soybean or egg yolk, despite the diverse market demands and high cost, owing to a tedious and inefficient manufacturing process. A microbial-based manufacturing process, specifically phospholipase D (PLD)-based biocatalysis and biotransformation process for PLs, has the potential to address several challenges associated with the soybean- or egg yolk-based supply chain. However, poor enzyme properties and inefficient microbial expression systems for PLD limit their wide industrial dissemination. Therefore, sourcing new enzyme variants with improved properties and developing advanced PLD expression systems are important. In the present review, we systematically summarize recent achievements and trends in the discovery, their structural properties, catalytic mechanisms, expression strategies for enhancing PLD production, and its multiple applications in the context of PLs. This review is expected to assist researchers to understand current advances in this field and provide insights for further molecular engineering efforts toward PLD-mediated bioprocessing.

Mining of a phospholipase D and its application in enzymatic preparation of phosphatidylserine.

Phosphatidylserine (PS) is useful as the additive in industries for memory improvement, mood enhancement and drug delivery. Conventionally, PS was extracted from soybeans, vegetable oils, egg yolk, and biomass; however, their low availability and high extraction cost were limiting factors. Phospholipase D (PLD) is a promising tool for enzymatic synthesis of PS due to its transphosphatidylation activity. In this contribution, a new and uncharacterized PLD was first obtained from GenBank database via genome mining strategy. The open reading frame consisted of 1614 bp and potentially encoded a protein of 538-amino-acid with a theoretical molecular mass of 60 kDa. The gene was successfully cloned and expressed in Escherichia coli. Its enzymatic properties were experimentally characterized. The temperature and pH optima of PLD were determined to be 60°C and 7.5, respectively. Its hydrolytic activity was improved by addition of Ca2+ at 5 mM as compared with the control. The enzyme displayed suitable transphosphatidylation activity and PS could be synthesized with L-serine and soybean lecithin as substrates under the catalysis of PLD. This PLD enzyme might be a potential candidate for industrial applications in PS production. To the best of our knowledge, this is the first report on genome mining of PLDs from GenBank database.

Ferrerol overcomes the invasiveness of lung squamous cell carcinoma cells by regulating the expression of inducers of Epithelial Mesenchymal Transition.

In recent years Epithelial Mesenchymal Transition (EMT) has been proposed as a mechanism indispensable to acquisition of metastatic properties by tumor cells. In this study we tested the ability of Ferrerol, a Chinese herb-derived compound to ablate the EMT in human lung squamous cell carcinoma cells. Human lung squamous cell carcinoma cells, Calu-1 were treated with various concentrations of Ferrerol for 24 h to examine its effect on their viability by the MTT assay. Only those concentrations which showed least effect on the viability of Calu-1 cells were further used to evaluate the expression of epithelial and mesenchymal markers by western blotting. Furthermore the effect of such concentrations on the migration and invasion of Calu-1 cells was determined by wound healing and transwell invasion assays respectively. The results demonstrated that Ferrerol treatment led to the downregulation of Slug and Zeb-1, transcriptional regulators of EMT with the concomitant increase and decrease in the expression of E-cadherin and vimentin respectively. These data were further supported by migration and invasion assays which demonstrated that Ferrerol treatment caused inhibited the migration and invasion of Calu-1 lung squamous cell carcinoma cells. Taken together, our results indicate that Ferrerol suppresses lung squamous cell carcinoma cell metastatic potential by modulating the expression of EMT proteins.

Nursing of prevention of phlebitis caused by vein medication Amiodarone Hydrochloride / 中国生化药物杂志

Objective To research and analyze nursing measures of phlebitis caused by vein medication Amiodarone Hydrochloride. Methods 150 arrhythmias patients in the Traditional Chinese. Medicine Hospital of Wenling were selected as the subjects. The control group was given routine transfusion nursing, the experimental group was given comprehensive nursing intervention on the basis of the control group, saline irrigation before and after transfusion, observed the local reaction of patients, and controlled the concentration and external application of potato chips. Results After the corresponding nursing measures, in the control group, accounting for 46.7%. 35 cases of phlebitis occurred in the experimental group. The incidence of phlebitis in the experimental group was 16.0%, which was significantly lower than that (46.7%) in the control group, which was statistically significant (P<0.05). In the experimental group, the number of patients with I degree phlebitis was 8, and the proportion was 66.67%. In the control group, there were 7 cases of I degree phlebitis, accounting for 20%, which was statistically significant (P<0.05). In the experimental group, there were 4 cases of II degree phlebitis, the proportion was 33.33%, significantly lower than that (54.28%) of the control group (19 cases of II degree phlebitis) with statistical significance (P<0.05). Conclusion The application of comprehensive nursing measures in arrhythmia patients treated with Amiodarone Hydrochloride vein medication, could significantly reduce the occurrence of phlebitis and improve the curative effect with high safety and clinical significance.

Nursing of prevention of phlebitis caused by vein medication Amiodarone Hydrochloride / 中国生化药物杂志

Objective To research and analyze nursing measures of phlebitis caused by vein medication Amiodarone Hydrochloride. Methods 150 arrhythmias patients in the Traditional Chinese. Medicine Hospital of Wenling were selected as the subjects. The control group was given routine transfusion nursing, the experimental group was given comprehensive nursing intervention on the basis of the control group, saline irrigation before and after transfusion, observed the local reaction of patients, and controlled the concentration and external application of potato chips. Results After the corresponding nursing measures, in the control group, accounting for 46.7%. 35 cases of phlebitis occurred in the experimental group. The incidence of phlebitis in the experimental group was 16.0%, which was significantly lower than that (46.7%) in the control group, which was statistically significant (P<0.05). In the experimental group, the number of patients with I degree phlebitis was 8, and the proportion was 66.67%. In the control group, there were 7 cases of I degree phlebitis, accounting for 20%, which was statistically significant (P<0.05). In the experimental group, there were 4 cases of II degree phlebitis, the proportion was 33.33%, significantly lower than that (54.28%) of the control group (19 cases of II degree phlebitis) with statistical significance (P<0.05). Conclusion The application of comprehensive nursing measures in arrhythmia patients treated with Amiodarone Hydrochloride vein medication, could significantly reduce the occurrence of phlebitis and improve the curative effect with high safety and clinical significance.

Effect of breviscapine against hepatic ischemia reperfusion injury.

BACKGROUND: Breviscapine is an active ingredient extracted from traditional Chinese medicine Erigeron breviscapus. The purpose of this study was to investigate the effect of breviscapine injection on hepatic ischemia and/or reperfusion injury. METHODS: Forty rats were randomly divided into five groups (n = 8): Sham group, Ischemia reperfusion 1 (I/R1) + normal saline (NS) group, I/R1 + breviscapine (Bre), I/R2 + NS group, and I/R2 + Bre group. Group1 and group2 represent ischemia time for 10 min and 30 min, respectively. Breviscapine or normal saline was administered to rats (single dose of 10 mg/Kg, intravenously) 30 min before hepatic ischemia. Serum transaminases, histopathologic changes, malondialdehyde (MDA), and superoxide dismutase (SOD) in liver tissues were evaluated. The expression level of mitochondrial fusion 2 (Mfn2) was also investigated. RESULTS: After 24-h reperfusion, based on the histopathologic analysis, compared with NS control group, the liver function was improved in breviscapine group. Liver enzymes aspartate and alanine aminotransferase levels were significantly lower in the I/R + Bre group, when compared with the I/R + NS group. Pretreatment with breviscapine reduced MDA level (P < 0.05) and increased SOD activity significantly in I/R + Bre compared with I/R + NS group. Western blot and RT-q polymerase chain reaction showed that Mfn2 was significantly downregulated in breviscapine preconditioning group as compared to normal saline control group. CONCLUSIONS: Breviscapine preconditioning attenuates liver ischemia reperfusion injury via inhibiting liver oxidative stress reaction. The protective mechanism probably inhibits Mfn2 protein and mRNA expression.

ZiBuPiYin recipe protects db/db mice from diabetes-associated cognitive decline through improving multiple pathological changes.

Multiple organ systems, including the brain, which undergoes changes that may increase the risk of cognitive decline, are adversely affected by diabetes mellitus (DM). Here, we demonstrate that type 2 diabetes mellitus (T2DM) db/db mice exhibited hippocampus-dependent memory impairment, which might associate with a reduction in dendritic spine density in the pyramidal neurons of brain, Aß1-42 deposition in the prefrontal cortex (PFC) and hippocampus, and a decreased expression of neurostructural proteins including microtubule-associated protein (MAP2), a marker of dendrites, and postsynaptic density 95 (PSD95), a marker of excitatory synapses. To investigate the effects of the ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine recipe, on diabetes-related cognitive decline (DACD), db/db mice received daily administration of ZBPYR over an experimental period of 6 weeks. We then confirmed that ZBPYR rescued learning and memory performance impairments, reversed dendritic spine loss, reduced Aß1-42 deposition and restored the expression levels of MAP2 and PSD95. The present study also revealed that ZBPYR strengthened brain leptin and insulin signaling and inhibited GSK3ß overactivity, which may be the potential mechanism or underlying targets of ZBPYR. These findings conclude that ZBPYR prevents DACD, most likely by improving dendritic spine density and attenuating brain leptin and insulin signaling pathway injury. Our findings provide further evidence for the effects of ZBPYR on DACD.

Optimization of total polysaccharide extraction from Herba Lophatheri using RSM and antioxidant activities.

Effects of extraction temperature, extraction time and ratio of water to material as well as their interactions on the yield of total polysaccharide from Herba lophatheri were studied by response surface methodology (RSM). The optimal conditions for the extraction of polysaccharides were determined to be the ratio of liquid to solid of 39.01, extraction time of 2.11h and extraction temperature of 97.09°C. Under these optimal conditions, the yield of polysaccharides obtained was 5.73±0.10%, which was well matched with the value predicted by the model. In vitro antioxidant assays showed that the polysaccharides HLP possessed significant inhibitory effects on superoxide radical. It also exhibited strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities, hydroxyl radical scavenging activities and its reducing power, ferrous ions chelating effect was also strong. These results suggested that H. lophatheri polysaccharides could be a suitable natural antioxidant and may be the functional foods for humans.

Warming with an underbody warming system reduces intraoperative hypothermia in patients undergoing laparoscopic gastrointestinal surgery: a randomized controlled study.

BACKGROUND: Intraoperative hypothermia is a common event during laparoscopic abdominal surgery. On one hand, intraoperative hypothermia can delay the metabolism and prevent tissue damage. One the other hand, long-term and severe intraoperative hypothermia may also lead to perioperative complications, such as increasing of peripheral resistance, coagulation dysfunction, intraoperative hemorrhage and postoperative shivering. Maintenance of normothermia during surgical procedures may improve the quality of patient care. OBJECTIVES: This study investigated the feasibility and efficacy of intraoperative cutaneous warming with an underbody warming system during laparoscopic gastrointestinal surgery. METHODS: 110 patients undergoing laparoscopic surgery for gastrointestinal cancer between January and December 2011 were randomized into the laparoscopic control (Control) group and laparoscopic intervention (Intervention) group. Nasopharyngeal temperature, prothrombin time, activated partial thromboplastin time, and thrombin time were measured before and during surgery, intraoperative and postoperative complications, as well as shivering after anesthesia and visual analog scale score for pain evaluation after surgery were also recorded. Clinical risk factors that may cause intraoperative hypothermia during laparoscopic surgery were also analyzed by correlation analysis. RESULTS: The two groups were comparable at the baseline. Intraoperative hypothermia was observed in 29 patients (52.7%) in Control group and 3 (5.5%) in Intervention group. Nasopharyngeal temperature in Control group was significantly decreased since 30min after the start of operation until the end of surgery comparing to that at the start of anesthesia, but there was no difference in the Intervention group. In Intervention group, the nasopharyngeal temperature was remaining at ∼36.5°C, indicating the feasibility and efficiency of the underbody warming system in preventing intraoperative hypothermia during laparoscopic gastrointestinal surgery. Moreover, with anesthesia and operation time increased, there was no significant change of coagulation function, hemoglobin level as well as less intraoperative hemorrhage, less postoperative shivering and lower visual analog scale score in Intervention group comparing to Control group. Multivariate logistic regression analysis revealed that anesthesia time and volume of CO2 were independent risk factors for perioperative hypothermia. CONCLUSIONS: Cutaneous warming with an underbody warming system is a feasible and effective method to prevent intraoperative hypothermia during laparoscopic gastrointestinal surgery.

In vitro antioxidant activities of polysaccharides extracted from Moso Bamboo-Leaf.

The objective of this study was to evaluate in vitro antioxidant capacities of polysaccharides extracted from Moso Bamboo-Leaf (BLP). The molecular weight of the polysaccharides were obtained by SEC-LLS and their molecular masses were 13.4×10(4)Da, 2.8×10(4)Da and 1.9×10(4)Da, respectively. Available data obtained with in vitro models suggested WB1 (precipitated by 30% ethanol) showed significant inhibitory effects on superoxide radical, hydroxyl radical, DPPH radical and ferrous metal-chelating capacities. These results clearly establish the possibility that polysaccharides extracted from Moso Bamboo-Leaf could be effectively employed as ingredient in health or functional food, to alleviate oxidative stress.

Oocyte quality in lactating dairy cows fed on high levels of n-3 and n-6 fatty acids.

Different fatty acid (FA) sources are known to influence reproductive hormones in cattle, yet there is little information on how dietary FAs affect oocyte quality. Effects of three dietary sources of FAs (supplying predominantly palmitic and oleic, linoleic (n-6) or linolenic (n-3) acids) on developmental potential of oocytes were studied in lactating dairy cows. A total of 12 Holstein cows received three diets containing rumen inert fat (RIF), soyabean or linseed as the main FA source for three periods of 25 days in a Latin-square design. Within each period, oocytes were collected in four ovum pick-up sessions at 3-4 day intervals. FA profiles in plasma and milk reflected profiles of dietary FA sources, but major FAs in granulosa cells were not affected. Dietary FA source did not affect plasma concentrations of leptin, insulin, IGF1, GH, or amino acids. RIF led to a higher proportion of cleaved embryos than soya or linseed, but blastocyst yield and embryo quality were not affected. It is concluded that the ovary buffers oocytes against the effects of fluctuations in plasma n-3 and n-6 FAs, resulting in only modest effects on their developmental potential.

Impact of dietary fatty acids on oocyte quality and development in lactating dairy cows.

The purpose of this study was to examine the effects of level of rumen inert fatty acids on developmental competence of oocytes in lactating dairy cows. Estrous cycles were synchronized in 22 cows on a silage-based diet supplemented with either low (200 g/day) or high (800 g/day) fat. A total of 1051 oocytes were collected by ultrasound-guided ovum pickup (OPU) in seven sessions/cow at 3-4 day intervals. Oocytes were matured, fertilized, and cultured to the blastocyst stage in vitro. Embryo quality was assessed by differential staining of Day 8 blastocysts. The high-fat diet reduced numbers of small and medium follicles. There was no effect on the quality of oocytes (grades 1-4) or cleavage rate. However, high fat significantly improved blastocyst production from matured (P < 0.005) and cleaved (P < 0.05) oocytes. Blastocysts from the high-fat group had significantly more total, inner cell mass and trophectoderm cells than the low-fat group (P < 0.05). Regression analysis showed negative effects of milk yield (P < 0.001), dry matter intake (P < 0.001), metabolizable energy intake (P < 0.005), and starch intake (P < 0.001) on blastocyst production in the low-fat group but not in the high-fat group. Within the low-fat group, blastocyst production was negatively related to growth hormone (P < 0.05) and positively related to leptin (P < 0.05). The low-fat group had higher nonesterified fatty acids than the high-fat group (P < 0.05). In conclusion, higher milk yields were associated with reduced developmental potential of oocytes in cows given a low-fat diet. Provision of a high-fat diet buffered oocytes against these effects, resulting in significantly improved developmental potential.