Most studies related to hemp are focused on Cannabidiol (CBD) and Tetrahydrocannabinol (THC); however, up to 120 types of phytocannabinoids are present in hemp. Hemp leaves contain large amounts of Cannabidiolic acid (CBDA) and Tetrahydrocannabinolic acid (THCA), which are acidic variants of CBD and THC and account for the largest proportion of CBDA. In recent studies, CBDA exhibited anti-hyperalgesia and anti-inflammatory effects. THCA also showed anti-inflammatory and neuroprotective effects that may be beneficial for treating neurodegenerative diseases. CBDA and THCA can penetrate the blood–brain barrier (BBB) and affect the central nervous system. The purpose of this study was to determine whether CBDA and THCA ameliorate Alzheimer’s disease (AD)-like features in vitro and in vivo. The effect of CBDA and THCA was evaluated in the Aβ_1–42-treated mouse model. We observed that Aβ_1–42-treated mice had more hippocampal Aβ and p-tau levels, pathological markers of AD, and loss of cognitive function compared with PBS-treated mice. However, CBDA- and THCA-treated mice showed decreased hippocampal Aβ and p-tau and superior cognitive function compared with Aβ_1–42-treated mice. In addition, CBDA and THCA lowered Aβ and p-tau levels, alleviated calcium dyshomeostasis, and exhibited neuroprotective effects in primary neurons. Our results suggest that CBDA and THCA have anti-AD effects and mitigate memory loss and resilience to increased hippocampal Ca²⁺, Aβ, and p-tau levels. Together, CBDA and THCA may be useful therapeutic agents for treating AD.

The association between adverse effects of PPI and gut microbiota in old age has yet to be elucidated. We assessed changes in the gut microbiota and butyrate levels following the long-term administration of PPIs to old rats and investigated their associations. F344 aged male rats were fed a PPI-supplemented diet for 50 weeks. The ileal microbiota was analysed by metagenomic sequencing of the 16S rRNA, while the butyrate concentration was measured by high-performance liquid chromatography. We observed a significant decrease in microbial diversity following PPI administration in the 2-year-old rats but not in the 74-week-old rats. PPI treatment reduced both commensal bacteria and opportunistic pathogens, particularly in the 2-year-old rats. Enterotypes comprising the majority of the control samples were enriched in Lactobacillus, while other enterotypes in the PPI group were dominated by Turicibacter or Romboutsia. The PPI treatment reduced the butyrate concentrations in the intestines and colons of 74-week-old rats compared to the control group. The abundance of Lactobacillus significantly correlated with butyrate concentrations in 74-week-old rats. In conclusion, long-term administration of PPIs alters the gut microbiota and butyrate concentrations in rats, particularly in old age, which may be an underlying mechanism of PPI-induced adverse effects such as pseudomembranous colitis.

Summary: Faecalibacterium prausnitzii ( F . prausnitzii ) is one of the most abundant bacteria in the human intestine, with its anti‐inflammatory effects establishing it as a major effector in human intestinal health. However, its extreme sensitivity to oxygen makes its cultivation and physiological study difficult. F . prausnitzii produces butyric acid, which is beneficial to human gut health. Butyric acid is a short‐chain fatty acid (SCFA) produced by the fermentation of carbohydrates, such as dietary fibre in the large bowel. The genes encoding butyryl‐CoA dehydrogenase (BCD) and butyryl‐CoA:acetate CoA transferase (BUT) in F . prausnitzii were cloned and expressed in E. coli to determine the effect of butyric acid production on intestinal health using DSS‐induced colitis model mice. The results from the E. coli Nissle 1917 strain, expressing BCD, BUT, or both, showed that BCD was essential, while BUT was dispensable for producing butyric acid. The effects of different carbon sources, such as glucose, N ‐acetylglucosamine (NAG), N ‐acetylgalactosamine (NAGA), and inulin, were compared with results showing that the optimal carbon sources for butyric acid production were NAG, a major component of mucin in the human intestine, and glucose. Furthermore, the anti‐inflammatory effects of butyric acid production were tested by administering these strains to DSS‐induced colitis model mice. The oral administration of the E. coli Nissle 1917 strain, carrying the expression vector for BCD and BUT (EcN‐BCD‐BUT), was found to prevent DSS‐induced damage. Introduction of the BCD expression vector into E. coli Nissle 1917 led to increased butyric acid production, which improved the strain’s health‐beneficial effects.

Cannabidiol (CBD), a primary constituent in hemp and cannabis, exerts broad pharmacological effects against various diseases, including cancer. Additionally, cabozantinib, a potent multi-kinase inhibitor, has been approved for treating patients with advanced hepatocellular carcinoma (HCC). Recently, there has been an increase in research on combination therapy using cabozantinib to improve efficacy and safety when treating patients. Here, we investigated the effect of a combination treatment of cabozantinib and CBD on HCC cells. CBD treatment enhanced the sensitivity of HCC cells to cabozantinib-mediated anti-cancer activity by increasing cytotoxicity and apoptosis. Phospho-kinase array analysis demonstrated that the apoptotic effect of the combination treatment was mainly related to p53 phosphorylation regulated by endoplasmic reticulum (ER) stress when compared to other kinases. The inhibition of p53 expression and ER stress suppressed the apoptotic effect of the combination treatment, revealing no changes in the expression of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-8, or cleaved caspase-9. Notably, the effect of the combination treatment was not associated with cannabinoid receptor 1 (CNR1) and the CNR2 signaling pathways. Our findings suggest that the combination therapy of cabozantinib and CBD provides therapeutic efficacy against HCC.

Porcine reproductive and respiratory syndrome (PRRS) poses a significant challenge in the global swine industry, leading to substantial economic losses and reproductive and respiratory complications. The causative agent, PRRS virus (PRRSV), with its high mutation rate, complicates the development of universally effective vaccines. Furthermore, current PRRS vaccines are limited by high costs and complex administration methods. Therefore, in this study, we aimed to develop an innovative Bacillus subtilis spore-based oral vaccine targeting PRRS. Their oral administration was evaluated in mice and pigs, and blood, saliva, feces, and bronchoalveolar lavage fluid samples were collected for further analyses. Our vaccine induced IgG and IgA immune responses in both models, with swine demonstrating considerable increase in specific antibody and cytokine levels. These results indicate a high potential for more effective and economically viable control of PRRS in commercial pig farming. The ease of administration and cost-effectiveness of the vaccine also offer a feasible option for widespread application. Our results suggest a new direction in veterinary vaccine development, underscoring the potential of B. subtilis spores in creating effective vaccines for large-scale, real-world applications in animal health management.