作者: Omran, Ziad ; Daqeeq, Abdullah H ; Burnet, Philip W J ; Blundell, Tom L ; Beaudoin, Christopher A ; van Tonder, Andries J ; Hala, Sharif ; Norget, Shannon

AbstractSimilarity between candidate drug targets and human proteins is commonly assessed to minimize the occurrence of side effects. Although numerous drugs have been found to disrupt the health of the human microbiome, no comprehensive comparison between established drug targets and the human microbiome metaproteome has yet been conducted. Therefore, herein, sequence and structure alignments between human and pathogen drug targets and representative human gut, oral, and vaginal microbiome metaproteomes were performed. Both human and pathogen drug targets were found to be similar in sequence, function, structure, and drug binding capacity to proteins in diverse pathogenic and non-pathogenic bacteria from all three microbiomes. The gut metaproteome was identified as particularly susceptible overall to off-target effects. Certain symptoms, such as infections and immune disorders, may be more common among drugs that non-selectively target host microbiota. These findings suggest that similarities between human microbiome metaproteomes and drug target candidates should be routinely checked.

2025-05-01·Radiology Case Reports

Patellar fracture nonunion treated without reosteosynthesis: Case report

Article

作者: Ismail, Abeer O ; Alqawlaq, Abdulelah K ; Maddah, Mohammad

Patellar fractures are common injuries often managed with open reduction and internal fixation (ORIF); however, nonunion is a rare complication, with an incidence of 2.4%-12.5%. This case report describes a 26-year-old male who sustained a comminuted patellar fracture in a road traffic accident and subsequently developed nonunion despite having a good range of motion and normal extension strength. He presented with persistent knee pain, and imaging confirmed the nonunion. Surgical removal of tension band wiring and cerclage was performed, revealing strong fibrous connections between the fracture fragments, and reosteosynthesis was deemed unnecessary. Postoperatively, the patient experienced complete pain relief and full functional recovery. This case highlights the importance of individualized treatment plans, demonstrating that not all cases of patellar nonunion require reosteosynthesis if the extensor mechanism remains intact, and that hardware removal alone can be an effective treatment strategy.

2025-04-01·The American Journal of Human Genetics

Bi-allelic pathogenic variants in TRMT1 disrupt tRNA modification and induce a neurodevelopmental disorder

Article

作者: Zamani, Mina ; Chatron, Nicolas ; Tümer, Zeynep ; Sabine, Sigaudy ; Bauer, Peter ; Fry, Andrew E ; Li, Chumei ; Rivier-Ringenbach, Clotilde ; Cabet, Sara ; Houlden, Henry ; Sidlow, Rich ; Lin, Renee ; Bereketoğlu, Muhammed Burak ; Abdullah, Uzma ; Varshney, Gaurav K ; Petree, Cassidy ; Sunnetci-Akkoyunlu, Deniz ; Bozdoğan, Sevcan Tuğ ; Maroofian, Reza ; Rønde, Gitte ; Bothe, Viktoria ; Gerkes, Erica H ; Jahnke, Friederike ; Julia, Sophie ; Mankad, Kshitij ; Rees, Mark I ; Nourbakhsh, Pardis ; Owrang, Daniel ; Kaiyrzhanov, Rauan ; Tran-Mau-Them, Frederic ; Zhang, Kejia ; Frykholm, Carina ; Rahner, Nils ; Sabri, Alihossein ; Banneau, Guillaume ; Chung, Wendy K ; Matsson, Hans ; Phornphutkul, Chanika ; Afzal, Erum ; Alvi, Javeria Raza ; Derrick, Anna V ; Yilmaz, Halil I ; Philippe, Christophe ; O'Connor, Mary ; Isidor, Bertrand ; Fu, Dragony ; Leo, Cailyn P ; Carere, Deanna Alexis ; Turchetti, Valentina ; Zaki, Maha S ; Sidpra, Jai ; Pehlivan, Davut ; Rad, Aboulfazl ; Hamid, Mohammad ; Hjortshøj, Tina D ; Yoon, Grace ; Wieczorek, Dagmar ; Gezdirici, Alper ; Kurul, Semra Hiz ; Soydemir, Didem ; Jacquemont, Marie-Line ; Suri, Mohnish ; Ashoori, Saeed ; Karagoz, Irem ; Koch-Hogrebe, Margarete ; Baig, Shahid Mahmood ; Azizimalamiri, Reza ; Sultan, Tipu ; Chung, Seo-Kyung ; Fleischer, Julie ; Bisgin, Atil ; Platzer, Konrad ; Thuresson, Ann-Charlotte ; Vona, Barbara ; Parvas, Sahere ; Galehdari, Hamid ; Kara, Bulent ; Glazunova, Olga O ; Reunert, Janine ; Tajudin, Tajul Arifin ; Scardamaglia, Annarita ; Deng, Chenghong ; Oprea, Gabriela ; Chamanrou, Niloofar ; Morrow, Michelle M ; Abumansour, Iman Sabri ; Shariati, Gholamreza ; Gleeson, Joseph G ; Marquardt, Thorsten ; Calame, Daniel G ; Zeighami, Jawaher ; Sedaghat, Alireza ; Benke, Paul J ; Lesca, Gaetan ; Zifarelli, Giovanni ; Cheema, Huma Arshad ; Efthymiou, Stephanie ; Huang, Kevin ; Valenzuela-Palafoll, Maria ; Lin, Sheng-Jia

The post-transcriptional modification of tRNAs plays a crucial role in tRNA structure and function. Pathogenic variants in tRNA-modification enzymes have been implicated in a wide range of human neurodevelopmental and neurological disorders. However, the molecular basis for many of these disorders remains unknown. Here, we describe a comprehensive cohort of 43 individuals from 31 unrelated families with bi-allelic variants in tRNA methyltransferase 1 (TRMT1). These individuals present with a neurodevelopmental disorder universally characterized by developmental delay and intellectual disability, accompanied by variable behavioral abnormalities, epilepsy, and facial dysmorphism. The identified variants include ultra-rare TRMT1 variants, comprising missense and predicted loss-of-function variants, which segregate with the observed clinical pathology. Our findings reveal that several variants lead to mis-splicing and a consequent loss of TRMT1 protein accumulation. Moreover, cells derived from individuals harboring TRMT1 variants exhibit a deficiency in tRNA modifications catalyzed by TRMT1. Molecular analysis reveals distinct regions of TRMT1 required for tRNA-modification activity and binding. Notably, depletion of Trmt1 protein in zebrafish is sufficient to induce developmental and behavioral phenotypes along with gene-expression changes associated with disrupted cell cycle, immune response, and neurodegenerative disorders. Altogether, these findings demonstrate that loss of TRMT1-catalyzed tRNA modifications leads to intellectual disability and provides insight into the molecular underpinnings of tRNA-modification deficiency caused by pathogenic TRMT1 variants.

项与 International Medical Center 相关的新闻（医药）

2023-01-15

·SYNAPSE

Dallah Healthcare Company Announces the Completion of the Procedures of the Acquisition of Shares in International Medical Center Company

Dallah Healthcare Company ("Dallah") announces the completion of the procedures for the acquisition of shares in International Medical Center Company. The completion of the procedure of acquiring the entire shares of Kun Investment Holding Company (hereinafter referred to as the "Selling Shareholder of IMC") in the capital of International Medical Center Company, which equals to fourteen million, two hundred thirty-two thousand and six hundred ninety (14,232,690) ordinary shares, representing 18.98% of the capital of International Medical Center Company, in exchange for the issuance of new shares in the Dallah to the Selling Shareholder of IMC, whereby the capital of Dallah will be increased from nine hundred million Saudi Riyals (SAR 900,000,000) to nine hundred seventy-six million, eight hundred eleven thousand and six hundred sixty Saudi Riyals (SAR 976,811,660) through the issuance of seven million, six hundred eighty-one thousand and one hundred sixty-six (7,681,166) new ordinary shares, thus increasing the total number of DHC's shares from ninety million (90,000,000) ordinary shares to ninety-seven million, six hundred eighty-one thousand and one hundred sixty-six (97,681,166) ordinary shares, representing an increase of about 8.53% of the Capital of DHC. Following the completion of the acquisition of the shares in International Medical Center Company, Dallah’s ownership percentage will be 27.18%. It should be noted that the Acquisition includes the following Related Parties: Dallah Al-Baraka Holding Company (as a substantial shareholder in the Dallah); Abdullah Saleh Kamel for being: (i) the Chairman and the substantial shareholder (directly and indirectly) in Dallah Al-Baraka Holding Company, and (ii) the sole shareholder of the Selling Shareholder of IMC; Muhei Addein Saleh Kamel for being the Vice-Chairman of the Dallah and the brother of Abdullah Saleh Kamel; and Mohamed Nabil Hefni for being: (i) a director in the Company; (ii) the CEO of the Selling Shareholder of IMC; and (iii) a director in International Medical Center Company*. It is worth noting that Mohamed Nabil Hefni resigned from the board of directors of International Medical Center Company as part of the conditions required to complete the acquisition. The financial impact will be visible on the financial results starting from the first quarter of the fiscal year 2023G.

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