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The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads. NAF-derived EXs (NAF-EXs) were used for loading ormeloxifene (ORM), a potent anti-cancer and desmoplasia inhibitor as a model drug. We found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype, which may be due to regulation of Ca2+ influx in fibroblast cells. NAF-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition (EMT) and repressed tumor growth in xenograft mouse model. In conclusion, our data suggests preferential tropism of NAF-EXs for PDAC tumors, thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer drugs. Additionally, it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.

The probiotic-derived siderophore, ferrichrome, enhances anti-tumor immunity and improves the efficacy of checkpoint immunotherapy in a model of pancreatic cancer by repolarizing tumor-associated macrophages to a immunostimulatory M1 phenotype.

Background: The whole of humanity has suffered dire consequences related to the novel coronavirus disease 2019 (COVID-19). Vaccination of the world base population is considered the most promising and challenging approach to achieving herd immunity. As healthcare organizations took on the extensive task of vaccinating the entire U.S. population, digital health companies expanded their automated health platforms in order to help ease the administrative burdens of mass inoculation. Although some software companies offer free applications to large organizations, there are prohibitive costs for small clinics such as the Good Health Associates Clinic (GHAC) for integrating and implementing new self-scheduling software into our e-Clinical Works (ECW) Electronic Health Record (EHR). These cost burdens resulted in a search that extended beyond existing technology, and in investing in new solutions to make it easier, more efficient, more cost-effective, and more scalable. Objective: In comparison to commercial entities, primary care clinics (PCCs) have the advantage of engaging the population for vaccination through personalized continuity of clinical care due to good rapport between their patients and the PCC team. In order to support the overall national campaign to prevent COVID-19 infections and restore public health, the GHAC wanted to make COVID-19 vaccination accessible to its patients and to the communities it serves. We aimed to achieve a coordinated COVID-19 vaccination drive in our community through our small primary care clinic by developing and using an easily implementable, cost-effective self-registration and scheduling web-based mobile platform, using the principle of “C.D.S. Five Rights”. Results: Overall, the Moderna vaccination drive using our developed self-registration and scheduling web portal and SMS messaging mobile platform improved vaccination uptake (51%) compared to overall vaccination uptake in our town, county (36%), and state (39%) during April–July 2021. Conclusions: Based on our experience during this COVID-19 vaccination drive, we conclude that PCCs have significant leverage as “invaluable warriors”, along with government and media education available, to engage patients for vaccination uptake; this leads to national preventive health spread in our population, and reduces expenses related to acute illness and hospitalization. In terms of cost-effectiveness, small PCCs are worthy of government-sponsored funding and incentives, including mandating EHR vendors to provide free (or minimal fee) software for patient self-registration and scheduling, in order to improve vaccination drive access. Hence, improved access to personalized informative continuity of clinical care in the PCC setting is a “critical link” in accelerating similar cost-effective campaigns in patient vaccine uptake.

Pancreatic cancer has the worst prognosis and lowest survival rate among all cancers. Pancreatic cancer cells are highly metabolically active and typically reprogrammed for aberrant glucose metabolism; thus they respond poorly to therapeutic modalities. It is highly imperative to understand mechanisms that are responsible for high glucose metabolism and identify natural/synthetic agents that can repress glucose metabolic machinery in pancreatic cancer cells, to improve the therapeutic outcomes/management of pancreatic cancer patients. We have identified a glycoside, steviol that effectively represses glucose consumption in pancreatic cancer cells via the inhibition of the translation initiation machinery of the molecular components. Herein, we report that steviol effectively inhibits the glucose uptake and lactate production in pancreatic cancer cells (AsPC1 and HPAF-II). The growth, colonization, and invasion characteristics of pancreatic cancer cells were also determined by in vitro functional assay. Steviol treatment also inhibited the tumorigenic and metastatic potential of human pancreatic cancer cells by inducing apoptosis and cell cycle arrest in the G1/M phase. The metabolic shift by steviol was mediated through the repression of the phosphorylation of mTOR and translation initiation proteins (4E-BP1, eIF4e, eIF4B, and eIF4G). Overall, the results of this study suggest that steviol can effectively suppress the glucose metabolism and translation initiation in pancreatic cancer cells to mitigate their aggressiveness. This study might help in the design of newer combination therapeutic strategies for pancreatic cancer treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has disrupted social and economic life globally. The global pandemic COVID-19 caused by this novel SARS-CoV-2 shows variable clinical manifestations, complicated further by cytokine storm, co-infections, and coagulopathy, leading to severe cases and death. Thrombotic complications arise due to complex and unique interplay between coronaviruses and host cells, inflammatory response, and the coagulation system. Heparin and derivatives are World Health Organization (WHO) recommended anticoagulants for moderate and severe Corona Virus Disease 19 (COVID-19), that can also inhibit viral adhesion to the cell membrane by interfering with heparan sulfate-dependent binding to angiotensin-converting enzyme 2 (ACE2) receptor. Heparin also possesses anti-inflammatory, immunomodulatory, antiviral, and anti-complement activity, which offers a benefit in limiting viral and microbial infectivity and anticoagulation from the immune-thrombosis system. Here we present a case study of the pathophysiology of unexpected COVID-19 coagulopathy of an obese African American patient. While being on therapeutic warfarin since admission, he had a dismal outcome due to cardio-pulmonary arrest after the sudden rise in D-dimer value from 1.1 to >20. This indicates that for such patients on chronic warfarin anticoagulation with “moderate COVID 19 syndromes”, warfarin anticoagulation may not be suitable compared to heparin and its derivatives. Further research should be done to understand the beneficial role of heparin and its derivatives compared to warfarin for COVID-19 inflicted patients.

Formalin-fixed paraffin embedded (FFPE) tissues are a valuable resource for biomarker discovery in order to understand the etiology of different cancers and many other diseases. Proteins are the biomarkers of interest with respect to FFPE tissues as RNA degradation is the major challenge in these tissue samples. Recently, non-protein coding transcripts, long non-coding RNAs (lncRNAs), have gained significant attention due to their important biological actions and potential involvement in cancer. RNA sequencing (RNA-seq) or quantitative reverse transcription-polymerase chain reaction (qRT-PCR) are the only validated methods to evaluate and study lncRNA expression and neither of them provides visual representation as immunohistochemistry (IHC) provides for proteins. We have standardized and are reporting a sensitive Z probe based in situ hybridization method to visually identify and quantify lncRNA in FFPE tissues. This assay is highly sensitive and identifies transcripts visible within different cell types and tumors. We have detected a scarcely expressed tumor suppressor lncRNA NRON (non-coding repressor of nuclear factor of activated T-cells (NFAT)), a moderately expressed oncogenic lncRNA UCA1 (urothelial cancer associated 1), and a highly studied and expressed lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript 1) in different cancers. High MALAT1 staining was found in colorectal, breast and pancreatic cancer. Additionally, we have observed an increase in MALAT1 expression in different stages of colorectal cancer.