Article
Virology
Gaohui Sun, Yaqun Sui, Yang Zhou, Junlin Ya, Cai Yuan, Longguang Jiang, Mingdong Huang
Summary: SARS-CoV-2 enters host cells through the serine protease transmembrane protease serine 2 (TMPRSS2), and camostat may prevent viral spread by inhibiting TMPRSS2 activity, but the specific mechanism is unclear.
JOURNAL OF VIROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Noora Barzkar, Zahoor Khan, Saeid Tamadoni Jahromi, Sajjad Pourmozaffar, Mohsen Gozari, Reza Nahavandi
Summary: Marine organisms are valuable sources of enzymes and their inhibitors with great therapeutic potential, particularly serine proteases and their inhibitors showing promise in biomedical applications. The uncontrolled activity of these proteases can lead to diseases, but their actions are regulated by serine protease inhibitors to maintain physiological functions.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Pharmacology & Pharmacy
Yutaka Kakizoe, Terumasa Nakagawa, Yasunobu Iwata, Qinyuan Deng, Masataka Adachi, Yoshikazu Miyasato, Miyuki Nakagawa, Yu Nagayoshi, Kayo Nishiguchi, Yuki Narita, Yuichiro Izumi, Takashige Kuwabara, Kimio Tomita, Kenichiro Kitamura, Masashi Mukoyama
Summary: In this study, the synthetic serine protease inhibitor, camostat mesilate (CM), was found to increase urine volume and promote free water excretion in healthy rats. The administration of CM also led to downregulation of AQP2 activity in the collecting duct, resulting in diuretic effects independent of renal medulla osmolality.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Teruhiko Mizumoto, Yutaka Kakizoe, Terumasa Nakagawa, Yasunobu Iwata, Yoshikazu Miyasato, Kohei Uchimura, Masataka Adachi, Qinyuan Deng, Manabu Hayata, Jun Morinaga, Taku Miyoshi, Yuichiro Izumi, Takashige Kuwabara, Yoshiki Sakai, Kimio Tomita, Kenichiro Kitamura, Masashi Mukoyama
Summary: The study demonstrated that camostat mesilate (CM) could exert renoprotective effects in MetS model rats, along with inhibiting podocyte apoptosis. These findings suggest that serine protease inhibition may become a new therapeutic strategy against MetS-related hypertension and renal injuries.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2021)
Review
Medicine, Research & Experimental
E. Burchacka, P. Pieta, A. Lupicka-Slowik
Summary: There are four types of antifungal drugs targeting different aspects of fungi, but increasing resistance poses a challenge to treatment options. Thus, developing new drug strategies is crucial for addressing fungal diseases effectively.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Immunology
Xin Zhang, Miao Li, Layla El Moussawi, Sally Saab, Shasha Zhang, Mike A. Osta, Kristin Michel
Summary: Humoral immune responses in animals are tightly controlled by regulated proteolysis, where extracellular protease cascades activate key immune proteins and enzymes. In mosquitoes, the protease network regulates melanization reactions and affects resistance against microorganisms.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Hannah Ceuleers, Nikita Hanning, Michelle De Bruyn, Joris G. De Man, Heiko U. De Schepper, Qian Li, Liansheng Liu, Steven Abrams, Annemieke Smet, Jurgen Joossens, Koen Augustyns, Ingrid De Meester, Pankaj J. Pasricha, Benedicte Y. De Winter
Summary: This study aimed to investigate the efficacy of serine protease inhibition on visceral pain in different animal models and explore the protease profiling. The results showed that serine protease inhibitors significantly reduced visceral hypersensitivity in the animal models and altered proteolytic activity in acute colitis. This study provided evidence for serine protease inhibitors as a promising therapeutic strategy for abdominal pain in gastrointestinal diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anssi Nikkola, Kari Antero Makela, Karl-Heinz Herzig, Shivaprakash Jagalur Mutt, Aishwarya Prasannan, Hanna Seppaenen, Terho Lehtimaki, Mika Kahonen, Olli Raitakari, Ilkka Seppala, Pihla Pakkanen, Isto Nordback, Juhani Sand, Johanna Laukkarinen
Summary: SPINK1 mutation has a significant impact on the development of acute alcohol pancreatitis (AAP) and is more prevalent in heavy alcohol users.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Jimin Hwang, Natalie Strange, Rami Mazraani, Matthew J. Phillips, Allan B. Gamble, Wilhelmina M. Huston, Joel D. A. Tyndall
Summary: A new series of CtHtrA inhibitors were developed by proline ring expansion and Cg-substitutions, which showed significantly improved antichlamydial activity in vitro.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Gillian A. Kelly-Robinson, James A. Reihill, Fionnuala T. Lundy, Lorcan P. McGarvey, John C. Lockhart, Gary J. Litherland, Keith D. Thornbury, S. Lorraine Martin
Summary: COPD is a complex disease characterized by unregulated proteolytic destruction of lung tissue mediated via a protease-antiprotease imbalance. Serpins, including AAT, play a crucial role in regulating protease activity in the lungs and understanding their physiological/pathological role could lead to new therapeutic opportunities for COPD and other chronic lung diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Tahsin F. Kellici, Ewa S. Pilka, Michael J. Bodkin
Summary: Serpins, a large and diverse family of proteins, play a crucial role in regulating inflammation, coagulation, thrombosis, thrombolysis, and immune responses. Recent advances in research on small-molecule modulators of serpins, their mode of action, and potential therapeutic perspectives are discussed, highlighting the importance of continued research in this field.
DRUG DISCOVERY TODAY
(2021)
Article
Nutrition & Dietetics
Ahmed Bakillah, Fatimah Al Hejji, Abdulrahman Almasaud, Haya Al Jami, Abbas Hawwari, Ali Al Qarni, Jahangir Iqbal, Naif Khalaf Alharbi
Summary: Lipid rafts rich in membrane cholesterol play a crucial role in the entry of SARS-CoV-2 into target cells. Depletion of cholesterol in these rafts increases SARS-CoV-2 entry, while exogenous cholesterol replenishment reverses this effect. Disturbance of intracellular cholesterol homeostasis also reduces viral entry.
Article
Chemistry, Medicinal
Patrick Gonschorek, Alessandro Zorzi, Tamara Maric, Mathilde Le Jeune, Mischa Schuettel, Mathilde Montagnon, Rebeca Gomez-Ojea, Denis Patrick Vollmar, Chantal Whitfield, Luc Reymond, Vanessa Carle, Hitesh Verma, Oliver Schilling, Alain Hovnanian, Christian Heinis
Summary: In this study, selective and high-affinity inhibitors of KLK5 and KLK7 were identified using phage display. The stability and half-life of the inhibitors were improved by eliminating proteaseprone sites and conjugating them to an albumin-binding peptide. These inhibitors were shown to reach the target KLKs in mouse epidermis and have the potential to control deregulated protease activity in Netherton syndrome.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Xiaoliang Wang, Damjan Avsec, Ales Obreza, Shida Yousefi, Irena Mlinaric-Rascan, Hans-Uwe Simon
Summary: This study demonstrates that serine protease inhibitors can block necrosis triggered by CD44, preventing cell death in GM-CSF-primed neutrophils. The inhibitors inhibit the activation of MLKL, p38 MAPK, and PI3K. However, they have no effect on apoptosis mediated by the FAS receptor.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Antony Cheudjeu
Summary: This article explores the significance of D-xylose in combating viruses, particularly SARS-CoV-2, which utilize core proteins as receptors on cell surfaces. It provides additional evidence supporting the theory of viral binding at HS/CS attachment sites and discusses how serine protease inhibitors inhibit viral entry. Additionally, it delves into the biosynthesis of HS, CS, DS, and Hep, initiated by D-xylose, and its potential role in the development of type 2 diabetes during viral infections. Studies on the correlation between D-xylose and COVID-19 severity are also addressed.
Article
Endocrinology & Metabolism
Qi Jin, Ni Shi, Desmond Aroke, Dong Hoon Lee, Joshua J. Joseph, Macarius Donneyong, Darwin L. Conwell, Phil A. Hart, Xuehong Zhang, Steven K. Clinton, Zobeida Cruz-Monserrate, Theodore M. Brasky, Rebecca Jackson, Lesley F. Tinker, Simin Liu, Lawrence S. Phillips, Aladdin H. Shadyab, Rami Nassir, Wei Bao, Fred K. Tabung
Summary: The study suggests that reducing the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.
Article
Gastroenterology & Hepatology
Mitchell L. Ramsey, Luis F. Lara, Cheryl E. Gariepy, Maisam Abu-El-Haija, Phil A. Hart, Alice Hinton, Stephen E. Kirkby, Somashekar G. Krishna, Susan S. Li, Darwin L. Conwell
Summary: The average age of hospitalized CF patients is increasing, and adults with CF are more likely to develop age-related comorbidities. In 2017, over 65% of CF hospitalizations occurred in individuals over 18 years old.
Article
Surgery
Brandon K. Chu, Bipul Gnyawali, Jordan M. Cloyd, Phil A. Hart, Georgios I. Papachristou, Luis F. Lara, Jeffrey R. Groce, Alice Hinton, Darwin L. Conwell, Somashekar G. Krishna
Summary: This study investigated reasons for early readmissions within 30 days after same-admission cholecystectomy for mild acute biliary pancreatitis. The study identified potentially modifiable risk factors and causes for early readmission, highlighting opportunities to improve clinical care for these patients.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2022)
Review
Gastroenterology & Hepatology
Phil A. Hart, David Bradley, Darwin L. Conwell, Kathleen Dungan, Somashekar G. Krishna, Kathleen Wyne, Melena D. Bellin, Dhiraj Yadav, Dana K. Andersen, Jose Serrano, Georgios I. Papachristou
Summary: Diabetes represents a group of diseases involving persistent hyperglycaemia, with exocrine disorders of the pancreas increasingly recognized as a potential cause or precursor. The pathophysiology of diabetes following acute pancreatitis is poorly understood and likely multifactorial.
LANCET GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Mitchell L. Ramsey, Yevgeniya Gokun, Lindsay A. Sobotka, Michael R. Wellner, Kyle Porter, Stephen E. Kirkby, Susan S. Li, Georgios I. Papachristou, Somashekar G. Krishna, Peter P. Stanich, Phil A. Hart, Darwin L. Conwell, Luis F. Lara
Summary: The study found that CFTR modulator use is associated with a reduction in AP hospitalizations among patients with cystic fibrosis, with a greater benefit observed in patients with pancreas-sufficient CF.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Gastroenterology & Hepatology
Soren S. Olesen, Anna E. Phillips, Mahya Faghih, Louise Kuhlmann, Emily Steinkohl, Jens B. Frokjaer, Benjamin L. Bick, Mitchell L. Ramsey, Phil A. Hart, Pramod K. Garg, Vikesh K. Singh, Dhiraj Yadav, Asbjorn M. Drewes
Summary: This study suggests that factors contributing to pain in chronic pancreatitis patients may overlap and have cumulative effects on patient-reported outcomes (PROs). Psychological distress had the strongest impact on PROs. Multidisciplinary strategies for pain management are recommended to address these findings.
Article
Dermatology
Jacob Nosewicz, Natalie Spaccarelli, Kristen M. Roberts, Phil A. Hart, Jessica A. Kaffenberger, John C. Trinidad, Benjamin H. Kaffenberger
Summary: Nutritional dermatoses may be underdiagnosed in developed countries like the United States, leading to increased morbidity and utilization of hospital resources. Dermatologists play a critical role in the diagnosis and management of patients with nutritional deficiencies, as they often present with cutaneous findings.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Dermatology
Jacob Nosewicz, Natalie Spaccarelli, Kristen M. Roberts, Phil A. Hart, Jessica A. Kaffenberger, John C. Trinidad, Benjamin H. Kaffenberger
Summary: Dermatologists play a critical role in diagnosing and managing nutritional deficiencies, which often manifest with skin findings. In the United States, common risk factors include chronic liver disease, alcoholism, and psychiatric disease. However, nutritional dermatoses may be under diagnosed in the United States, leading to increased morbidity and hospital resource utilization. Therefore, it is necessary for providers in developed nations to identify these deficiencies and provide relevant context to dermatologists.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Anna Evans Phillips, Mahya Faghih, Vikesh K. Singh, Soren Schou Olesen, Louise Kuhlmann, Srdan Novovic, Benjamin Bick, Philip A. Hart, Mitchell L. Ramsey, Rupjyoti Talukdar, Pramod K. Garg, Dhiraj Yadav, Asbjorn Mohr Drewes
Summary: An international consortium was formed to better understand and characterize chronic pancreatitis pain through standardized sensory testing. The consortium successfully developed a P-QST nomogram, which identified chronic pancreatitis patients with widespread hyperalgesia as having higher pain intensity scores and decreased quality of life. Multiple studies are ongoing to validate these findings and assess their utility in clinical trials.
Article
Gastroenterology & Hepatology
Peter Madril, Paige Golian, Marcia Nahikian-Nelms, Alice Hinton, Philip A. Hart, Kristen M. Roberts
Summary: In a cohort of pancreatic diseases patients, 18% were identified as at risk for malnutrition, with gastrointestinal symptoms being more common in this group. While nutrition consultation rates increased, 66% of at-risk patients did not receive clearly indicated dietary evaluation or management recommendations.
Article
Gastroenterology & Hepatology
Pedram Paragomi, Georgios I. Papachristou, Kwonho Jeong, Alice Hinton, Ioannis Pothoulakis, Rupjyoti Talukdar, Rakesh Kochhar, Mahesh K. Goenka, Aiste Gulla, Jose A. Gonzalez, Vikesh K. Singh, Miguel Ferreira Bogado, Tyler Stevens, Sorin T. Barbu, Haq Nawaz, Silvia C. Gutierrez, Narcis Zarnescu, Livia Archibugi, Jeffrey J. Easler, Konstantinos Triantafyllou, Mario Pelaez-Luna, Shyam Thakkar, Carlos Ocampo, Enrique de-Madaria, Gregory A. Cote, Bechien U. Wu, Peter J. Lee, Phil A. Hart, Darwin L. Conwell, Frederico G. S. Toledo, Dhiraj Yadav
Summary: This study examined the impact of pre-existing diabetes mellitus on the severity of acute pancreatitis and found that pre-existing diabetes mellitus itself is not a risk factor for severe acute pancreatitis.
Review
Gastroenterology & Hepatology
Furqan A. Bhullar, Mahya Faghih, Venkata S. Akshintala, Ahmed I. Ahmed, Katie Lobner, Elham Afghani, Anna E. Phillips, Phil A. Hart, Mitchell L. Ramsey, Benjamin L. Bick, Louise Kuhlmann, Asbjorn M. Drewes, Dhiraj Yadav, Soren S. Olesen, Vikesh K. Singh
Summary: This systematic review aimed to determine the prevalence of primary painless chronic pancreatitis (CP). The analysis of published studies revealed that approximately one in ten patients with CP have primary painless disease, with the majority being attributable to idiopathic/genetic etiology.
Article
Cell Biology
Kristyn Gumpper-Fedus, Phil A. Hart, Martha A. Belury, Olivia Crowe, Rachel M. Cole, Valentina Pita Grisanti, Niharika Badi, Sophia Liva, Alice Hinton, Christopher Coss, Mitchell L. Ramsey, Anne Noonan, Darwin L. Conwell, Zobeida Cruz-Monserrate
Summary: Cachexia occurs in up to 80% of pancreatic ductal adenocarcinoma (PDAC) patients, with higher levels of oleic acid and lower levels of linoleic acid observed in cachexia patients. Lauric and eicosapentaenoic acids are positively correlated with age in cachexia patients. Subjects with diabetes have lower palmitic:oleic acid ratios. Linoleic acid levels are lower in subjects with diabetes and correlated with hemoglobin and albumin in subjects with cachexia.
Article
Gastroenterology & Hepatology
Stephen A. Firkins, Phil A. Hart, Georgios I. Papachristou, Luis F. Lara, Zobeida Cruz-Monserrate, Alice Hinton, Darwin L. Conwell, David P. Bradley, Somashekar G. Krishna
Summary: The study used a population-based database to evaluate predictors of new-onset diabetes mellitus after acute pancreatitis, finding that increasing age, male sex, lower income, comorbidities, components of metabolic syndrome, severe AP, and recurrent AP are independently associated with an increased risk of AP-related DM. These variables at a population level can help identify patients who may benefit from closer follow-up, intensive education, and preventative strategies.
Review
Gastroenterology & Hepatology
Antonio Facciorusso, Luca Barresi, Renato Cannizzaro, Filippo Antonini, Konstantinos Triantafyllou, Georgios Tziatzios, Nicola Muscatiello, Phil A. Hart, Sachin Wani
Summary: The diagnostic performance of EUS-guided tissue acquisition in patients with AIP is modest, with an improved performance of FNB compared to FNA.
ENDOSCOPY INTERNATIONAL OPEN
(2021)