C1q and TNF-related 1 (C1QTNF1/CTRP1) is an adiponectin-associated protein belonging to the C1q/TNF-related protein family. Recent studies have shown that the C1q and TNF-related protein (CTRP) family is involved in cancer progression; however, the specific role of CTRP1 in tumor progression has not yet been elucidated. To examine the role of CTRP1 in tumor progression, we generated CTRP1 knockout A549 and HCT116 cell lines, which reduced the expression levels of nuclear factor (NF)-κB-dependent and metastasis-promoting transcripts. We demonstrated that CTRP1 knockout inhibited the cell proliferation and invasion and tumor growth. Finally, database analysis showed that CTRP1 expression was upregulated in metastatic cancers and elevated levels of CTRP1 were associated with poor prognosis. These results suggest that CTRP1 expression contributes to NF-κB signaling and promotes tumor progression.

Previously, we reported that epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR1/ADGRE1) is abnormally expressed in colon cancer (CC) and is a risk factor for lymph node metastasis (LNM) and poor recurrence-free survival in patients with abundant tumor-associated macrophages (TAMs). However, the signaling pathways associated with EMR1 expression in CC progression remain unclear. In this study, we aimed to explore the role of EMR1 and its signaling interactions with macrophages in CC progression. Spatial transcriptomics of pT3 microsatellite unstable CC tissues revealed heightened Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in EMR1-HL CC with LNM compared to EMR1-N CC without LNM. Through in vitro coculture of CC cells with macrophages, EMR1 expression by CC cells was found to be induced by TAMs, ultimately interacting with upregulated JAK/STAT signaling, increasing cell proliferation, migration, and motility, and reducing apoptosis. JAK2/STAT3 inhibition decreased the levels of EMR1, JAK2, STAT1, and STAT3, significantly impeded the proliferation, migration, and mobility of cells, and increased the apoptosis of EMR1⁺ CC cells compared to their EMR1^KO counterparts. Overall, TAMs-induced EMR1 upregulation in CC cells may promote LNM and CC progression via JAK2/STAT1,3 signaling upregulation. This study provides further insights into the molecular mechanisms involving macrophages and intracellular EMR1 expression in CC progression, suggesting its clinical significance and offering potential interventions to enhance patient outcomes.

Coronavirus can cause various diseases, from mild symptoms to the recent severe COVID-19. The coronavirus RNA genome is frequently mutated due to its RNA nature, resulting in many pathogenic and drug-resistant variants. Therefore, many medicines should be prepared to respond to the various coronavirus variants. In this report, we demonstrated that Forsythia viridissima fruit ethanol extract (FVFE) effectively reduces coronavirus replication. We attempted to identify the active compounds and found that actigenin from FVFE effectively reduces human coronavirus replication. Arctigenin treatment can reduce coronavirus protein expression and coronavirus-induced cytotoxicity. These results collectively suggest that arctigenin is a potent natural compound that prevents coronavirus replication.

Immune-modulatory effects in obese-diabetes (db/db) mice were observed to understand the possible mechanism(s) of ephedrine-induced unfavorable responses. The ephedrine doses were selected based on the FDA report (NTP Tech Rep Ser NO 307; CAS# 134-72-5), which showed the non-toxic dose for B6C3F1 mice. In db/db mice, higher doses (6 and 12 mg/mouse) of ephedrine significantly harmed the liver and lung morphology, including fatty liver with multiple blood vessel engorgement, alveolar wall thickening, and inflammatory response in the lung. The immune micro-environment of db/db mice was an inflammatory state with suppressed adaptive cellular immunity. After the administration of ephedrine, significant deterioration of NK activity was observed with lowered gene transcription of klrk1 encoding NKG2D, and of ccl8, a NK cell targeting chemokine. Suppressed cellular immunity in db/db mice was lowered ever further by single ephedrine treatment, as was evidenced by mitogen-induced T or B cell proliferations. These observations demonstrate that at the non-toxic doses in normal B6C3F1 mice, ephedrine clearly suppressed systemic immunity of db/db mice. The data suggest that the immune micro-environment of obese individuals is fragile and susceptible to ephedrine-related pathologic response, and this may be a prelude to the induction of obesity-related secondary immunological disorders.

AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis, and AMPK contributes to cell growth, apoptosis, and autophagy. Although most cell studies have been performed using two-dimensional (2D) cell culture, recent studies have demonstrated that the three-dimensional (3D) spheroid technique is helpful in various cell research fields, such as tumor biology, due to its resemblance to the 3D tissue structure. However, the role of AMPK in 3D spheroid formation has not been characterized clearly. This study used the AMPK knockout cell line to examine the role of AMPK in 3D spheroid formation and is the first report describing the generation of 3D spheroids using AMPK knockout cells. While control cells produced round spheroids with a similar length-to-width ratio, AMPK knockout produced an oval shape with a more significant length-to-width ratio. We demonstrate that AMPK knockout spheroids contain significantly more prominent lysosomes in each cell, indicating that autophagic flux is impaired in 3D spheroids. Finally, flow cytometry analysis showed that AMPK knockout spheroids contain more apoptotic cells than control cells. These results indicate that AMPK is required for efficient 3D spheroid formation.