Peptic Ulcer

幽门螺旋杆菌（Helicobacter pylori，Hp）能够在人体胃部极端酸性环境中长期存活，其适应pH变化的能力至关重要。其中，酸反应双组分系统ArsRS构成了一种应对酸性环境的全局调控网络，然而，ArsRS如何精细调控转录过程的分子机制尚未得到充分解析。近日，一篇发表在国际杂志Nucleic Acids Research上题为“Molecular insights into the fine-tuning of pH-dependent ArsR-mediated regulation of the SabA adhesin in Helicobacter pylori”的研究报告中，来自于默奥大学等机构的科学家们通过研究，揭示了Hp与炎症性胃部组织相互作用的分子细节及其受胃部pH值调控的具体机制。研究人员指出，深入理解Hp如何在胃内建立持久、终身感染，对于识别触发疾病的关键特征至关重要。Hp感染一旦确立，若未经适当治疗，将持续终生，引发消化性溃疡乃至胃癌。胃内环境并非恒定，而是经历广泛的pH波动，从胃腔内的强酸环境到被粘液层保护的胃上皮细胞表面接近中性的微环境。Hp主要定殖于粘液层或紧贴上皮细胞外侧，其基因表达广泛受到pH感应调节，从而根据局部环境pH动态调整蛋白质产量。揭示pH值影响幽门螺旋杆菌在发炎胃部组织中粘附的分子机制图片来源：Nucleic Acids Research (2024). DOI:10.1093/nar/gkae188幽门螺旋杆菌的表面存在称之为粘附素（adhesins）的粘附蛋白，其往往作用于粘液层或最外层的细胞层，SabA蛋白就是其中一种粘附素，其能促使细菌粘附在发炎的胃粘膜上。这项研究中，研究人员在分子水平上阐明了pH是如何影响SabA蛋白的产生，在低pH下，调节性蛋白ArsR会被磷酸化并形成复合体。本文研究揭示了ArsR复合体的两个结合位点，并强调了DNA拓扑结构对于ArsR结合的重要性。此外，研究人员还识别出了pH调节ArsR蛋白复合体中的ArsR结合位点，研究者指出，不同幽门螺旋杆菌菌株之间特定的DNA区域的差异或许会影响pH调节的SabA表达。研究过程中，科研团队面临的主要技术挑战在于Hp的遗传改造。由于其基因结构复杂，这一过程既技术要求高又耗时颇多。尽管曾尝试委托国际专业公司进行设计，历经四个月多次尝试，最终未能成功。值得注意的是，Hp倾向于定植于胃底部，此处pH值较胃体中段略高，后者富含产酸细胞，导致更低的pH。长期研究已揭示胃体（胃中段）Hp感染与胃癌风险的关联。更深入理解pH如何影响Hp粘附等基本特性，将有助于揭示其何种特征更易引发疾病。综上所述，该研究揭示了酸性条件下ArsR-P精确抑制转录的关键分子机制，这种转录调控可能介导Hp在胃粘膜层定位的微妙变化，为深入理解Hp致病特性的研究奠定了重要基础。参考文献：Anna Åberg, Pär Gideonsson, Abhayprasad Bhat, et al. Molecular insights into the fine-tuning of pH-dependent ArsR-mediated regulation of the SabA adhesin in Helicobacter pylori, Nucleic Acids Research (2024). DOI:10.1093/nar/gkae188本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

Growing data shows intravenous ibuprofen is safe and effective for the treatment of pain and fever in adults, children and infants NASHVILLE, Tenn., April 2, 2024 /PRNewswire/ -- Cumberland Pharmaceuticals Inc. (Nasdaq: CPIX), a specialty pharmaceutical company, today announced the release of a Special Report evaluating the growing amount of current data supporting the use of its Caldolor® product (intravenous ibuprofen, or IVIB) as a standard of care for the treatment of pain and fever in adults, children and infants. The report, published in Anesthesiology News, General Surgery News and Pharmacy Practice News, highlights the need for the prudent and careful management of pain, particularly as the prescription of opioids for pain treatment has become commonplace, often leading to dependence and misuse. "My hope is that this Special Report will emphasize the use of Caldolor as a foundation for multimodal pain management, while also helping to address the opioid epidemic," said Michael W. Lew, M.D., Clinical Professor and Past Chair for the Department of Anesthesiology and Perioperative Medicine at the City of Hope Cancer Center. As part of a comprehensive safety and efficacy developmental plan, IVIB was studied in various treatment areas, including surgical pain, fever and nonsurgical acute pain. The results, which are highlighted in the report, show it's a safe and effective treatment for pain and fever in adults, children and infants as young as 3 months of age. Takeaways from the report note that: IVIB results in significant reduction in temperature compared with placebo (in adults) and with acetaminophen (in pediatric patients). Administration of the product prior to surgery leads to patients waking up in significantly less postsurgical pain, while also lessening or even eliminating the need for opioids. IVIB use in the hospital ED for acute pain can minimize opioid requirements, while achieving pain control. IVIB is the only non-opioid injectable analgesic approved for use in children as young as 3 months of age. IVIB should be considered a foundation for any multimodal pain regimen. "Pain management has become one of the most common health care problems," said A.J. Kazimi, CEO of Cumberland Pharmaceuticals. "As this new report states, comprehensive multimodal pain regimens have become key in preventing pain and optimizing pain control, while minimizing the need for opioids. A non-steroidal anti-inflammatory drug, or NSAID, such as Caldolor has become a cornerstone for many treatment paradigms, and we are continually encouraged by the growing database from our studies of the product in patients of all ages." To learn more about the clinical results demonstrated with IVIB and read the full report at . For full prescribing and safety information, visit . About Caldolor® Caldolor is indicated in adults and pediatric patients for the management of mild to moderate pain and the management of moderate to severe pain as an adjunct to opioid analgesics, as well as the reduction of fever. It was the first FDA-approved intravenous therapy for fever. Caldolor is contraindicated in patients with known hypersensitivity to ibuprofen or other NSAIDs as well as patients with a history of asthma or other allergic type reactions after taking aspirin or other NSAIDs. Caldolor is contraindicated for use during the peri-operative period in the setting of coronary artery bypass graft (CABG) surgery. For full prescribing and safety information, including boxed warning, visit . About Cumberland Pharmaceuticals Cumberland Pharmaceuticals Inc. is the largest biopharmaceutical company founded and headquartered in Tennessee and is focused on providing unique products that improve the quality of patient care. The company develops, acquires, and commercializes products for the hospital acute care, gastroenterology and oncology market segments. The company's portfolio of FDA-approved brands includes: Acetadote® (acetylcysteine) injection, for the treatment of acetaminophen poisoning; Caldolor® (ibuprofen) injection, for the treatment of pain and fever; Kristalose® (lactulose) oral, a prescription laxative, for the treatment of constipation; Omeclamox®-Pak, (omeprazole, clarithromycin, amoxicillin) oral, for the treatment of Helicobacter pylori (H. pylori) infection and related duodenal ulcer disease; Sancuso® (granisetron) transdermal, for the prevention of nausea and vomiting in patients receiving certain types of chemotherapy treatment; Vaprisol® (conivaptan) injection, to raise serum sodium levels in hospitalized patients with euvolemic and hypervolemic hyponatremia; and Vibativ® (telavancin) injection, for the treatment of certain serious bacterial infections including hospital-acquired and ventilator-associated bacterial pneumonia, as well as complicated skin and skin structure infections. The company also has a series of Phase II clinical programs underway evaluating its ifetroban product candidate in patients with cardiomyopathy associated with Duchenne Muscular Dystrophy, Systemic Sclerosis and Idiopathic Pulmonary Fibrosis. Investigational new study applications have been cleared by the FDA enabling Cumberland to launch clinical studies in each of these areas. For more information on Cumberland's approved products, including full prescribing information, please visit links to the individual product websites, which can be found on the company's website at . Forward Looking Statements This press release contains forward-looking statements, which are subject to certain risks and reflect Cumberland's current views on future events based on what it believes are reasonable assumptions. No assurance can be given that these events will occur. Forward-looking statements include, among other things, statements regarding the company's intent, belief or expectations, and can be identified by the use of terminology such as "may," "will," "expect," "believe," "intend," "plan," "estimate," "should," "seek," "anticipate," "look forward" and other comparable terms or the negative thereof. As with any business, all phases of Cumberland's operations are subject to factors outside of its control, and any one or combination of these factors could materially affect Cumberland's operation results. These factors include macroeconomic conditions, including rising interest rates and inflation, competition, an inability of manufacturers to produce Cumberland's products on a timely basis, failure of manufacturers to comply with regulations applicable to pharmaceutical manufacturers, natural disasters, public health epidemics, maintaining an effective sales and marketing infrastructure, and other events beyond the company's control as more fully discussed in its most recent annual report on Form 10-K as filed with the U.S. Securities and Exchange Commission (SEC), as well as the company's other filings with the SEC from time to time. There can be no assurance that results anticipated by the company will be realized or that they will have the expected effects. Readers are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date hereof. The company does not undertake any obligation to publicly revise these statements to reflect events after the date hereof. SOURCE Cumberland Pharmaceuticals Inc.

Nitrate patients subgroup demonstrated 100% correct self-selection when utilizing the web app technology with the drug facts label compared to 40% when using drug facts label alone (among 86% vs. 56% of all users) underscoring the significant potential benefits of technology assistance in an OTC setting (Please see important safety information below) NEW YORK, NY / ACCESSWIRE / April 2, 2024 / Petros Pharmaceuticals, Inc. (Nasdaq:PTPI), a company focused on expanding consumer access to medication through over-the- counter (OTC) drug development programs, announces positive results of an initial cohort of its self-selection study comparing the use of a Drug Facts Label (DFL) alone to a DFL in combination with a web app (technology component). Fady Boctor, Petros' President and Chief Commercial Officer, commented, "This two-arm study, intended to directionally demonstrate that use of a DFL-alone would be insufficient for self-selection, while the proposed technology provided significantly improved results. This trial serves as a preliminary version of our pivotal Phase 2 study that is currently in-field, initiated earlier this month. The pivotal study is designed to provide the FDA with compelling evidence showing that users are able to determine the appropriateness of STENDRA® (avanafil) without the need for a physician and prescription." In the 30-person study, approximately 86% of users of the DFL and technology component (Arm B) correctly self-selected, compared to only 56% of users who used the DFL alone (Arm A). These data are intended to provide directional evidence to further discussions with the U.S. Food and Drug Administration (FDA) regarding the need for the Additional Condition of Nonprescription Use (ACNU) in the form of the web app. Importantly, this initial study included a subgroup of nitrate users (n=9) who demonstrated 100% correct self-selection when using the app-technology (n=4) compared to only 40% of similar participants (n=5) in the DFL-only arm. "The positive results in this study are another step forward in our efforts to expand access to STENDRA to potentially become the first OTC prescription-grade therapeutic option for erectile dysfunction (ED). It is of particular importance that the subgroup of nitrate users, a population of high concern for the FDA, showed 100% correct self-selection, indicating the potential benefit of using this technology in combination with a DFL. It shows the potential for safe OTC availability even among this higher-risk group. We look forward to providing further updates on the ongoing pivotal, larger population study, toward which we look to have similar and robust results. Importantly, we continue to believe we have sufficient funding to achieve our development goals as well as significant near-term clinical milestones for STENDRA, added Mr. Boctor." As previously disclosed, the Company anticipates that in the event positive self-selection data are achieved following this study and the ongoing pivotal self-selection studies, and upon FDA study clearance, it would expeditiously initiate an actual use trial, akin to a Phase 3 registration trial in clinical development sequencing. About Petros Pharmaceuticals Petros Pharmaceuticals is committed to the goal of becoming a leading innovator in the emerging self-care market driving expanded access to key prescription pharmaceuticals as Over-the-Counter treatment options. Currently, Petros is pursuing increased access for its flagship prescription ED therapy, STENDRA, via potential OTC designation. If ultimately approved by the FDA for OTC access, STENDRA may be the first in its class to achieve this marketing status, also establishing company know how as a proven platform for other prospective prescription therapeutics. About the OTC Pathway The process of switching a prescription medication to over the counter (OTC) first involves the design of a Drug Facts Label (DFL) that is well understood by potential consumers. Then data must show that consumers can make an appropriate decision to use or not to use the product based only upon the information on the DFL and their personal medical history. Then consumers must demonstrate that they can properly use the product based upon the information on the DFL. To accomplish these things, the FDA ordinarily requires a consumer tested OTC DFL. This testing includes conduct of iterative Label Comprehension Studies (LCS) in the general population, Self-Selection Studies (SSS) in a population interested in using the product and in specific populations who may be harmed if they use the product, and usually one Actual Use Trial (AUT) demonstrating safe and appropriate use by consumers in a simulated OTC setting. The regulations that FDA is currently finalizing introduced Additional Conditions for Nonprescription Use (ACNU) criteria that enable correct self-selection by consumers and may expand OTC access to medications that formerly could only be available by prescription. An ACNU may be an innovative computerized tool, or the additional conditions may use other approaches that support the switch process. Important Safety Information about STENDRA® (avanafil) STENDRA® (avanafil), originally launched by Auxilium Pharmaceuticals prior to that company's sale to Endo Pharmaceuticals, is an oral phosphodiesterase 5 (PDE5) inhibitor for the treatment of erectile dysfunction. STENDRA is not for use in women or children. It is not known if STENDRA is safe and effective in women or children under 18 years of age. (A 100-mg and 200-mg tablet can be taken as early as ~15 minutes before sexual activity. STENDRA only works with sexual stimulation and should not be taken more than once a day. STENDRA can be taken with or without food; do not drink too much alcohol when taking STENDRA (for example, more than 3 glasses of wine or 3 shots of whiskey) as it can increase chances of side effects. Of people enrolled in clinical trials, 1.4%, 2.0%, and 2.0%, respectively, stopped taking STENDRA (50 mg, 100 mg, or 200 mg) due to side effects compared to 1.7% on placebo. STENDRA® was designed and developed expressly for erectile dysfunction. STENDRA is contraindicated with any form of organic nitrates, in patients with known hypersensitivity to any component of the tablet, and in patients who are using a guanylate cyclase stimulator. Patients should not use STENDRA if sexual activity is inadvisable due to cardiovascular status or any other reason. Before taking STENDRA tell your doctor if you have had any kind of heart issues including heart attack, heart failure, angina and irregular heartbeat or have elevated or low blood pressure. Use of STENDRA with alpha-blockers, other antihypertensives, or substantial amounts of alcohol (greater than 3 units) may lead to hypotension. Patients should seek emergency treatment if an erection lasts greater than 4 hours. Patients should stop STENDRA and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of Non Arteritic Ischemic Optic Neuropathy (NAION). Discuss with patients the increased risk of NAION in patients with a history of NAION. Patients should stop taking STENDRA and seek prompt medical attention in the event of sudden decrease or loss of hearing. STENDRA can potentiate the hypotensive effect of nitrates, alpha blockers, antihypertensives, and alcohol. CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, erythromycin) increase STENDRA exposure. For patients taking concomitant strong CYP3A4 inhibitors (including ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir and telithromycin), do not use STENDRA. Combination with Other PDE5 Inhibitors or Erectile Dysfunction Therapies is not recommended. The safety of STENDRA is unknown in patients with bleeding disorders and patients with active peptic ulceration. The use of STENDRA offers no protection against sexually transmitted diseases including HIV. Consider counseling patients on protective measures for sexually transmitted diseases. The most common adverse reactions reported with use of STENDRA include headache, flushing, nasal congestion, nasopharyngitis, and back pain. For more information about STENDRA, call 844-458-4887. If you would like to report an adverse event or product complaint, please contact us at 844-458-4887. You are encouraged to report negative side effects of prescription drugs to the FDA by calling 1-800-FDA-1088, or at . Please see the full Prescribing Information and Patient Information. Cautionary Note Regarding Forward-Looking Statements This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements are based upon Petros Pharmaceuticals, Inc.'s ("Petros," "we," "our," "us" or the "Company") management's assumptions, expectations, projections, intentions, and beliefs about future events. In some cases, predictive, future-tense or forward-looking words such as "intend," "develop," "goal," "plan," "predict", "may," "will," "project," "estimate," "anticipate," "believe," "expect," "continue," "potential," "opportunity," "forecast," "should," "target," "pursuit," "strategy" and similar expressions, whether in the negative or affirmative, that reflect our current views with respect to future events and operational, economic and financial performance are intended to identify forward-looking statements, but are not the exclusive means of identifying such statements. Such forward-looking statements are only predictions, and actual results and the timing of certain events and circumstances may differ materially from those described by the forward-looking statements as a result of risks and uncertainties, including, without limitation, Petros' ability to execute on its business strategy, including its plans to develop and commercialize its product candidates; Petros' ability to receive clearance from the FDA to sell STENDRA as an Over-the-Counter treatment; Petros' ability to comply with obligations as a public reporting company; Petros' ability to maintain compliance with the Nasdaq Stock Market's listing standards; risks related to Petros' ability to continue as a going concern; risks related to Petros' history of incurring significant losses; risks related to Petros' dependence on the commercialization of a single product, STENDRA®; and risks related to Petros' ability to obtain regulatory approvals for, or market acceptance of, any of its products or product candidates. Additional factors that could cause actual results to differ materially from the results anticipated in these forward-looking statements are contained in the Company's periodic reports and in other filings that the Company has or may file, with the U.S. Securities and Exchange Commission (the "SEC") under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere. The Company cautions readers that the forward-looking statements included in this press release represent our beliefs, expectations, estimates and assumptions only as of the date of hereof and are not intended to give any assurance as to future results. New factors emerge from time to time, and it is not possible for us to predict all these factors. Further, the Company cannot assess the effect of each such factor on our business or the extent to which any factor, or combination of factors, may cause actual results to be materially different from those contained in any forward-looking statement. Accordingly, you should not unduly rely on any forward-looking statements. The Company undertakes no obligation to update or revise any forward-looking statements contained in this press release, whether as a result of new information, future events, a change in our views or expectations or otherwise, except as required by federal securities laws. Contacts Investors: CORE IR ir@petrospharma.com Media: Jules Abraham CORE IR 917-885-7378 pr@coreir.com SOURCE: Petros Pharmaceuticals, Inc. View the original press release on accesswire.com