The present study was aimed to investigate the antinociceptive and anti-inflammatory activity of the Curcuma zedoaria (family Zingiberaceae) ethanolic rhizome extract in laboratory using both in vitro and in vivo methods so as to justify its traditional use in the above mentioned pathological conditions. Phytochemical screening was done to find the presence of various secondary metabolites of the plant. In vivo antinociceptive activity was performed employing the hot plate method, acidic acid induced writhing test and formalin induced writhing test on Swiss albino mice at doses of 250 and 500 mg/kg body weight. Anti-inflammatory activity test was done on Long Evans rats at two different doses (250 and 500 mg/kg body weight) by using carrageenan induced paw edema test. Finally in vitro anti-inflammatory test by protein-denaturation method was followed. Data were analyzed by one-way analysis of variance (ANOVA) and Dunnett’s t-test was used as the test of significance. P value <0.05 was considered as the minimum level of significance. Phytochemical screening revealed presence of tannins, saponins, flavonoids, gums & carbohydrates, steroids, alkaloids, reducing sugars and terpenoids in the extract. In the hot plate method, the extract increased the reaction time of heat sensation significantly to 61.99% and 78.22% at the doses of 250 and 500 mg/kg BW respectively. In acetic acid induced writhing test, the percent inhibition of writhing response by the extract was 48.28% and 54.02% at 250 and 500 mg/kg doses respectively (p < 0.001). The extract also significantly inhibited the licking response in both the early phase (64.49%, p < 0.01) and the late phase (62.37%, p < 0.01) in formalin induced writhing test. The extract significantly (p < 0.05, p < 0.01 and p < 0.001) inhibited carrageenan induced inflammatory response in rats in a dose related manner. In in-vitro anti-inflammatory test, the extract significantly inhibited protein denaturation of 77.15, 64.43, 53.04, 36.78 and 23.70% for doses of 500, 400, 300, 200 and 100 μg/mL respectively. The results obtained from the tests indicate that the plant might have one or more secondary metabolite(s) having central and peripheral analgesic and anti-inflammatory activity.

Human telencephalon is an evolutionarily advanced brain structure associated with many uniquely human behaviors and disorders. However, cell lineages and molecular pathways implicated in human telencephalic development remain largely unknown. We produce human telencephalic organoids from stem cell-derived single neural rosettes and investigate telencephalic development under normal and pathological conditions. We show that single neural rosette-derived organoids contain pallial and subpallial neural progenitors, excitatory and inhibitory neurons, as well as macroglial and periendothelial cells, and exhibit predictable organization and cytoarchitecture. We comprehensively characterize the properties of neurons in SNR-derived organoids and identify transcriptional programs associated with the specification of excitatory and inhibitory neural lineages from a common pool of NPs early in telencephalic development. We also demonstrate that neurons in organoids with a hemizygous deletion of an autism- and intellectual disability-associated gene SHANK3 exhibit intrinsic and excitatory synaptic deficits and impaired expression of several clustered protocadherins. Collectively, this study validates SNR-derived organoids as a reliable model for studying human telencephalic cortico-striatal development and identifies intrinsic, synaptic, and clustered protocadherin expression deficits in human telencephalic tissue with SHANK3 hemizygosity.

Probiotics are being used as feed/food supplements as an alternative to antibiotics. It has been demonstrated that probiotics provide several health benefits, including preventing diarrhea, irritable bowel syndrome, and immunomodulation. Alongside probiotic bacteria-fermented foods, the different structural components, such as lipoteichoic acids, teichoic acids, peptidoglycans, and surface-layer proteins, offer several advantages. Probiotics can produce different antimicrobial components, enzymes, peptides, vitamins, and exopolysaccharides. Besides live probiotics, there has been growing interest in consuming inactivated probiotics in farm animals, including pigs. Several reports have shown that live and killed probiotics can boost immunity, modulate intestinal microbiota, improve feed efficiency and growth performance, and decrease the incidence of diarrhea, positioning them as an interesting strategy as a potential feed supplement for pigs. Therefore, effective selection and approach to the use of probiotics might provide essential features of using probiotics as an important functional feed for pigs. This review aimed to systematically investigate the potential effects of lactic acid bacteria in their live and inactivated forms on pigs.

Nogo-A (Rtn 4A), a member of the reticulon 4 (Rtn4) protein family, is a neurite outgrowth inhibitor protein that is primarily expressed in the central nervous system (CNS). However, previous studies revealed that Nogo-A was upregulated in skeletal muscles of Amyotrophic lateral sclerosis (ALS) patients. Additionally, experiments showed that endoplasmic reticulum (ER) stress marker, C/EBP homologous protein (CHOP), was upregulated in gastrocnemius muscle of a murine model of ALS. We therefore hypothesized that Nogo-A might relate to skeletal muscle diseases. According to our knocking down and overexpression results in muscle cell line (C2C12), we have found that upregulation of Nogo-A resulted in upregulation of CHOP, pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while downregulation of Nogo-A led to downregulation of CHOP, IL-6 and TNF-α. Immunofluorescence results showed that Nogo-A and CHOP were expressed by myofibers as well as tissue macrophages. Since resident macrophages share similar functions as bone marrow-derived macrophages (BMDM), we therefore, isolated macrophages from bone marrow to study the role of Nogo-A in activation of these cells. Lipopolysaccharide (LPS)-stimulated BMDM in Nogo-KO mice showed low mRNA expression of CHOP, IL-6 and TNF-α compared to BMDM in wild type (WT) mice. Interestingly, Nogo knockout (KO) BMDM exhibited lower migratory activity and phagocytic ability compared with WT BMDM after LPS treatment. In addition, mice experiments data revealed that upregulation of Nogo-A in notexin- and tunicamycin-treated muscles was associated with upregulation of CHOP, IL-6 and TNF-α in WT group, while in Nogo-KO group resulted in low expression level of CHOP, IL-6 and TNF-α. Furthermore, upregulation of Nogo-A in dystrophin-deficient (mdx) murine model, myopathy and Duchenne muscle dystrophy (DMD) clinical biopsies was associated with upregulation of CHOP, IL-6 and TNF-α. To the best of our knowledge, this is the first study to demonstrate Nogo-A as a regulator of inflammation in diseased muscle and bone marrow macrophages and that deletion of Nogo-A alleviates muscle inflammation and it can be utilized as a therapeutic target for improving muscle diseases.

Life-long regeneration of healthy muscle by cell transplantation is an ideal therapy for patients with degenerative muscle diseases. Yet, obtaining muscle stem cells from patients is very limited due to their exhaustion in disease condition. Thus, development of a method to obtain healthy myogenic stem cells is required. Here, we showed that the four transcription factors, Six1, Eya1, Esrrb, and Pax3, converts fibroblasts into induced myogenic stem cells (iMSCs). The iMSCs showed effective differentiation into multinucleated myotubes and also higher proliferation capacity than muscle derived stem cells both in vitro and in vivo. The iMSCs do not lose their proliferation capacity though the passaging number is increased. We further isolated CD106-negative and α7-integrin-positive iMSCs (sort-iMSCs) showing higher myogenic differentiation capacity than iMSCs. Moreover, genome-wide transcriptomic analysis of iMSCs and sort-iMSCs, followed by network analysis, revealed the genes and signaling pathways associated with enhanced proliferation and differentiation capacity of iMSCs and sort-iMSCs, respectively. The stably expandable iMSCs provide a new source for drug screening and muscle regenerative therapy for muscle wasting disease.