Community-driven partnerships with Community-Engaged Research teams bring resources and reliable information to Baltimore residents.

This case study presents an analysis of community-driven partnerships, focusing on the nonprofit Baltimore CONNECT (BC) network and its collaborative efforts with a Community-Engaged Research (CEnR) team of the Johns Hopkins Institute for Clinical and Translational Research (ICTR). BC has built a network of over 30 community-based organizations to provide health and social services in Baltimore City. The study emphasizes the role of CEnR in supporting community-led decision-making, specifically in the planning and implementation of community health resource fairs.

Policy Insights from High-Income Countries to Guide Safe, Nutritious, and Sustainable Alternative Proteins for Low- and Middle-Income Countries.

The United Nations has encouraged governments to promote sustainable healthy diets to address undernutrition, obesity, and climate change. This perspective paper examines policy insights from selected high-income countries in Asia, Europe, and North America to understand how traditional and novel alternative proteins (AP) may support sustainable healthy diets in low- and middle-income countries (LMIC) where populations experience malnutrition in all forms. AP products must be affordable, locally sustainable, and culturally acceptable to improve diet quality and health.

Type II BMP and activin receptors BMPR2 and ACVR2A share a conserved mode of growth factor recognition.

BMPR2 is a type II Transforming Growth Factor (TGF)-β family receptor that is fundamentally associated with pulmonary arterial hypertension (PAH) in humans. BMPR2 shares functional similarities with the type II activin receptors ACVR2A and ACVR2B, as it interacts with an overlapping group of TGF-β family growth factors (GFs). However, how BMPR2 recognizes GFs remains poorly understood.

Smad2/3 Activation Regulates Smad1/5/8 Signaling via a Negative Feedback Loop to Inhibit 3T3-L1 Adipogenesis.

Adipose tissues (AT) expand in response to energy surplus through adipocyte hypertrophy and hyperplasia. The latter, also known as adipogenesis, is a process by which multipotent precursors differentiate to form mature adipocytes. This process is directed by developmental cues that include members of the TGF-β family.

P-Rex1 Mediates Glucose-Stimulated Rac1 Activation and Insulin Secretion in Pancreatic β-Cells.

Background/aims: Despite the published evidence implicating phosphoinositide 3-kinase (PI3-kinase) in the regulation of islet function, limited information is available on the putative contributory roles of its downstream signaling steps, including the phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1 (P-Rex1) signaling pathway in the islet β-cell. Therefore, we investigated potential roles for P-Rex1 in glucose-stimulated Rac1 activation and insulin secretion in insulin-secreting (INS-1 832/13) β-cells.

Methods: Glucose-stimulated Insulin secretion (GSIS) was quantified by ELISA.

Service learning in public health nursing education: How COVID-19 accelerated community-academic partnership.

Days after COVID-19 physical distancing precautions were implemented, a coalition of community leaders in Baltimore City founded the Baltimore Neighbors Network (BNN), a volunteer network established to provide proactive phone-based support to older adults in Baltimore City. BNN was a community-driven approach aimed at reducing social isolation and improving health equity both during the pandemic and long-term. This paper describes how the Johns Hopkins School of Nursing's (JHUSON) public health nursing clinical faculty and students partnered with BNN to support a community-driven crisis response effort while creatively meeting student learning objectives.

Paradoxical regulation of glucose-induced Rac1 activation and insulin secretion by RhoGDIβ in pancreatic β-cells.

Small GTPases (e.g., Rac1) play key roles in glucose-stimulated insulin secretion (GSIS) in the β-cell.

Quantitative proteomics reveals novel interaction partners of Rac1 in pancreatic β-cells: Evidence for increased interaction with Rac1 under hyperglycemic conditions.

Rac1, a small G protein, regulates physiological insulin secretion from the pancreatic β-cell. Interestingly, Rac1 has also been implicated in the onset of metabolic dysfunction of the β-cell under the duress of hyperglycemia (HG). This study is aimed at the identification of interaction partners of Rac1 in β-cells under basal and HG conditions.

Combination of Carmustine and Selenite Inhibits EGFR Mediated Growth Signaling in Androgen-Independent Prostate Cancer Cells.

Although aberrant androgen receptor (AR) signaling is a central mechanism for castration resistant prostate cancer (CRPC) progression, AR-independent growth signaling is also present in CRPC. The current therapeutic options for patients with CRPC are limited and new drugs are desperately needed to eliminate these crucial growth signaling pathways. We have previously shown that combination of carmustine and selenite effectively induces apoptosis and growth inhibition by targeting AR and AR-variants in CRPC cells.

Combination of carmustine and selenite effectively inhibits tumor growth by targeting androgen receptor, androgen receptor-variants, and Akt in preclinical models: New hope for patients with castration resistant prostate cancer.

Despite established androgen receptor (AR) antagonists, AR/AR-variants signaling remain a major obstacle for the successful treatment of castration resistant prostate cancer (CRPC). In addition, CRPC cells adapt to survive via AR-independent pathways to escape next generation therapies. Therefore, there is an urgent need for drugs that can target these signaling pathways in CRPC.

Oxalate at physiological urine concentrations induces oxidative injury in renal epithelial cells: effect of α-tocopherol and ascorbic acid.

Objectives: To test our hypothesis that physiological levels of urinary oxalate induce oxidative renal cell injury, as studies to date have shown that oxalate causes oxidative injury only at supra-physiological levels. To study the combined effect of α-tocopherol and ascorbic acid against oxalate-induced oxidative injury, as oxalate-induced oxidative cell injury is known to promote initial attachment of calcium oxalate crystals to injured renal tubules and subsequent development of kidney stones.

Materials And Methods: Cultures of normal (antioxidant-undepleted) and antioxidant-depleted LLC-PK1 cells were exposed to oxalate at human physiological urine concentrations.

Carmustine enhances the anticancer activity of selenite in androgen-independent prostate cancer cells.

Apoptosis is one of the major mechanisms targeted in the development of therapies against various cancers, including prostate cancer. Resistance to chemotherapy poses a significant problem for the effective treatment of androgen-independent (hormone-refractory) prostate cancer. Although high concentrations of sodium selenite exert strong anticarcinogenic effects in several cell culture systems and animal models, the therapeutic potential of selenite in patients with advanced or metastatic prostate cancer is extremely limited by the genotoxicity of high-dose selenite.

Inhibition of 5-lipoxygenase triggers apoptosis in prostate cancer cells via down-regulation of protein kinase C-epsilon.

Previous studies have shown that human prostate cancer cells constitutively generate 5-lipoxygenase (5-LOX) metabolites from arachidonic acid, and inhibition of 5-LOX blocks production of 5-LOX metabolites and triggers apoptosis in prostate cancer cells. This apoptosis is prevented by exogenous metabolites of 5-LOX, suggesting an essential role of 5-LOX metabolites in the survival of prostate cancer cells. However, downstream signaling mechanisms which mediate the survival-promoting effects of 5-LOX metabolites in prostate cancer cells are still unknown.

Selective Rac1 inhibition protects renal tubular epithelial cells from oxalate-induced NADPH oxidase-mediated oxidative cell injury.

Oxalate-induced oxidative cell injury is one of the major mechanisms implicated in calcium oxalate nucleation, aggregation and growth of kidney stones. We previously demonstrated that oxalate-induced NADPH oxidase-derived free radicals play a significant role in renal injury. Since NADPH oxidase activation requires several regulatory proteins, the primary goal of this study was to characterize the role of Rac GTPase in oxalate-induced NADPH oxidase-mediated oxidative injury in renal epithelial cells.

Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 β/β-catenin pathway.

Activation of survival pathways has been associated with chemoresistance and progression of androgen independence which places a major obstacle to successful treatment of metastatic prostate cancer. Deguelin, a rotenoid isolated from Mundulea sericea, has an anticancer effect against several types of cancers; however, the mechanism of its antitumor effects on prostate cancer is not well understood. The aim of our study was to elucidate the effect of deguelin on the growth of prostate cancer cells and its putative mechanism of action.

Oxalate-induced activation of PKC-alpha and -delta regulates NADPH oxidase-mediated oxidative injury in renal tubular epithelial cells.

Oxalate-induced oxidative stress contributes to cell injury and promotes renal deposition of calcium oxalate crystals. However, we do not know how oxalate stimulates reactive oxygen species (ROS) in renal tubular epithelial cells. We investigated the signaling mechanism of oxalate-induced ROS formation in these cells and found that oxalate significantly increased membrane-associated protein kinase C (PKC) activity while at the same time lowering cytosolic PKC activity.

A critical analysis of the role of gut Oxalobacter formigenes in oxalate stone disease.

Hyperoxaluria is a major risk factor for the formation of calcium oxalate stones, but dietary restriction of oxalate intake might not be a reliable approach to prevent recurrence of stones. Hence, other approaches to reduce urinary oxalate to manage stone disease have been explored. The gut-dwelling obligate anaerobe Oxalobacter formigenes (OF) has attracted attention for its oxalate-degrading property.

FAK association with multiple signal proteins mediates pressure-induced colon cancer cell adhesion via a Src-dependent PI3K/Akt pathway.

Cancer cell adhesion is traditionally viewed as random, occurring if the cell's receptors match the substrate. Cancer cells are subjected to pressure and shear during growth against a constraining stroma, surgical manipulation, and passage through the venous and lymphatic system. Cells shed into a cavity such as the abdomen postoperatively also experience increased pressure from postoperative edema.

Pressure stimulates breast cancer cell adhesion independently of cell cycle and apoptosis regulatory protein (CARP)-1 regulation of focal adhesion kinase.

Background: Pressure stimulates colon cancer adhesion via focal adhesion kinase (FAK). Extracellular pressures reaching 29 mm Hg have been reported in rapidly growing breast cancers, and tumors experience pressure during surgical manipulation. We hypothesized that pressure stimulates breast cancer adhesion and that CARP-1, which influences cancer biology, inhibits FAK, and modulates pressure effects.

Focal adhesion kinase protein levels in gut epithelial motility.

Mucosal healing requires migration and proliferation. Most studies of focal adhesion kinase (FAK), a protein that regulates motility, proliferation, and apoptosis, have focused on rapid phosphorylation. We reported lower FAK protein levels in motile Caco-2 colon cancer cells and postulated that this reduction in FAK available for activation might impact cell migration and mucosal healing.

Extracellular pressure stimulates tumor cell adhesion in vitro by paxillin activation.

Metastasizing colon cancer cells bind target tissues primarily via integrins. Extracellular pressure or shear stress stimulates integrin-mediated adhesion to matrix proteins or endothelial cells by activating the focal adhesion proteins FAK and Src. Because this effect is blocked by cytoskeletal perturbation and paxillin may link the cytoskeleton to the focal adhesion complex, we evaluated the role of paxillin in pressure-induced malignant colonocyte adhesion.

Paxillin modulates squamous cancer cell adhesion and is important in pressure-augmented adhesion.

Paxillin is an adapter protein regulating signaling and focal adhesion assembly that has been linked to malignant potential in many malignancies. Overexpression of paxillin has been noted in aggressive tumors. Integrin-mediated binding through the focal adhesion complex is important in metastatic adhesion and is upregulated by extracellular pressure in malignant colonocytes through FAK and Src activation.

Divalent cations influence colon cancer cell adhesion in a murine transplantable tumor model.

Background: Cancer cells adhere principally by integrins, matrix receptors that may be influenced by divalent cations. Surgical wound fluid is high in Mg2+ and low in Ca2+. We hypothesized that Mg+ and Mn2+ promote perioperative adhesion of shed cancer cells to surgical sites and that washing surgical wounds with Ca2+ inhibits implantation.

The role of the cytoskeleton in differentially regulating pressure-mediated effects on malignant colonocyte focal adhesion signaling and cell adhesion.

Increased extracellular pressure stimulates colon cancer cell adhesion by activating focal adhesion kinase (FAK) and Src. We investigated the role of the cytoskeleton in pressure-induced inside-out FAK and Src phosphorylation and pressure-stimulated adhesion. We perturbed actin polymerization with phalloidin, cytochalasin D and latrunculin B, and microtubule organization with colchicine and paclitaxol.

Extracellular pressure stimulates colon cancer cell adhesion in vitro and to surgical wounds by Src (sarcoma protein) activation.

Background: We hypothesized that pressure stimulates colon cancer cell adhesion to surgical wounds.

Methods: We quantitated adhesion of murine 26/51 transplantable colon cancer cells by cell counting or chromium 51-labeling. Tumor cells were added to murine surgical wounds after 30 minutes preincubation under ambient or 15 mm Hg increased pressure.