Discovery of biomarkers for diagnosis and therapeutic monitoring of complications in patients with thalassemia diseases

Goals 3
Ensure healthy lives and promote well-being for all at all ages

Discovery of biomarkers for diagnosis and therapeutic monitoring of complications in patients with thalassemia diseases

โรคธาลัสซีเมีย เป็นความผิดปกติทางพันธุกรรมในการสร้างโกลบิน ความผิดปกติดังกล่าวทำให้เม็ดเลือดแดงตัวอ่อนถูกทำลายตั้งแต่อยู่ในไขกระดูก มีกระบวนการสร้างเม็ดเลือดแดงที่ผิดปกติ เม็ดเลือดแดงที่ถูกสร้างขึ้นทั้งจำนวนและลักษณะรูปร่างมีความผิดปกติ ทำให้ผู้ป่วยมีภาวะซีด จึงเร่งการสร้างเซลล์เม็ดเลือดและการดูดซึมธาตุเหล็ก นอกจากนี้ การรักษาโดยการให้เลือดเพื่อลดภาวะซีด ส่งผลต่อภาวะเหล็กเกิน ภาวะเครียดระดับเซลล์ ก่อให้เกิดปัญหาด้านสุขภาพที่เกิดจากภาวะแทรกซ้อนต่าง ๆ ตามมา เช่น ภาวะตับม้ามโต ภาวะตัวเหลืองตาเหลือง ภาวะภูมิคุ้มกันบกพร่อง ความดันโลหิตสูง ภาวะหลอดเลือดอุดตันโดยเฉพาะที่ปอด โรคหัวใจล้มเหลว โรคหลอดเลือดสมอง ซึ่งเป็นสาเหตุสำคัญที่ทำให้ผู้ป่วยถึงแก่ชีวิต

 

การวินิจฉัยเพื่อติดตามผลของการรักษาและการเฝ้าระวังการเกิดภาวะแทรกซ้อนต่าง ๆ ในผู้ป่วยโรคธาลัสซีเมียยังไม่มีตัวบ่งชี้ทางชีวภาพที่ ง่าย ราคาถูก รวดเร็ว เที่ยงตรงและมีความแม่นยำสูง ดังนั้น คณะผู้วิจัย จึง มุ่งเน้นการค้นหาตัวบ่งชี้ทางชีวภาพสำหรับตรวจวินิจฉัยและติดตามการรักษาภาวะแทรกซ้อนต่าง ๆ ในผู้ป่วยโรคธาลัสซีเมียที่สามารถใช้ได้ในโรงพยาบาลระดับปฐมภูมิ เพื่อเพิ่มขีดความสามารถทางการแพทย์ในการบ่งชี้การเกิดโรคตั้งแต่ระยะเริ่มต้น

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Identify pathways that promote the toxicity of anti-malarial medicine for the development of novel therapeutics against malaria

Goals 3
Ensure healthy lives and promote well-being for all at all ages

Identify pathways that promote the toxicity of anti-malarial medicine for the development of novel therapeutics against malaria

Artemisinin and its derivatives are among the front line drugs for malarial treatment due to their high efficacy and minimal side effects.  In addition and perhaps most importantly, artemisinins are also active against parasites that are resistant to other types of anti-malarial drugs.  Although the exact molecular basis of artemisinin-mediated toxicity remains unclear and despite the efforts to prevent the development of artemisinin resistance using combination therapies, many studies have shown that artemisinin resistance in malaria parasites has already emerged.  Our study aims to enhance the understanding of the basic molecular processes involved in the anti-malarial activity of artemisinin which can assist in the design of artemisinin based anti-malarial combination therapies to prevent the emergence of drug resistance as well as aid in the development of novel therapeutics against malaria.

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Aspartyl protease inhibition interferes with Plasmodium falciparum asexual blood‑stage and early gametocyte development

Goals 3
Ensure healthy lives and promote well-being for all at all ages

Aspartyl protease inhibition interferes with Plasmodium falciparum asexual blood‑stage and early gametocyte development

Plasmodium falciparum can cause severe illness and mortality, especially in pregnant women and young children. Asexual stage and gametocyte cause harmful manifestations to the patients and contribute to the spread of the disease, respectively. Moreover, most recent therapeutic drugs did not affect the gametocyte. The discovery of a new drug with dual actions on both stages could elucidate a cost-effective way to combat malaria. Within a human host, the parasite possesses many activities for its survival, such as invasion, haemoglobin degradation, and protein trafficking, many of which are related to aspartyl protease, revealing the potential for antimalarial drug targets. To demonstrate the effects of pepstatin A, a board-spectrum aspartyl protease inhibitor, the number of parasites with stage distribution and morphological changes were evaluated under the microscope. Pepstatin A at 100 μM inhibited the asexual stage and early-stage gametocyte development by 47% and 73%, respectively. They exhibited morphological defects, including chromatin condensation, vacuolization and haemozoin clumping in both asexual blood-stage and early-stage gametocyte. However, it could not influence the late-stage gametocyte development and gamete formation. Inconclusion, pepstatin A moderately affected both asexual blood-stage and early-stage gametocyte development. Morphological changes on treated parasites implied the effect of pepstatin A on haemoglobin degradation, suggesting its potential for reducing the severity of the disease and minimizing malaria transmission. However, further research and development are required to use aspartyl protease as a drug target, focusing on identifying and modifying the drug to be more sensitive and effective.

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Growth Inhibition and Additive Effect to Antimalarial Drugs of Brucea javanica Extracts on Asexual Blood-Stage Plasmodium falciparum

Goals 3
Ensure healthy lives and promote well-being for all at all ages

Growth Inhibition and Additive Effect to Antimalarial Drugs of Brucea javanica Extracts on Asexual Blood-Stage Plasmodium falciparum

Malaria is a parasitic infectious disease that is endemic in many tropical countries. Even though several effective antimalarial agents have been implemented, treatment failure still occurs, and malaria continues to cause neurological complications and death, particularly in severe or drug-resistant cases. Hence, novel therapeutic agents with distinct mechanisms of action, as well as alternative chemical compounds that can overcome resistance, are still needed to improve malaria therapy. This study aimed to investigate the antimalarial activities of Brucea javanica extracts against Plasmodium falciparum, the major species associated with severe malaria. In this study, malaria parasites were treated with plant extracts using single and co-incubation methods, along with artesunate and chloroquine, and their inhibitory effect on parasite development was determined by microscopy. The results show that all tested doses of the extracts that effectively inhibited malaria parasites did not cause hemolysis of red blood cells. The root extract and fruit extract inhibited parasite growth at IC50 values of 0.41 ± 1.14 μg/mL and 0.26 ± 1.15 μg/mL, respectively. These extracts significantly interrupted malaria development at the ring stage. The defective parasites treated with plant extracts were characterized by nuclear clumping, leading to pyknotic cell death. Moreover, these extracts elicited an additive effect with artesunate and chloroquine, significantly reducing IC90 levels for the inhibition of parasite development. In conclusion, B. javanica extracts inhibited the asexual blood-stage development of malaria parasites. They distinctively show the additive effects of ATS and CRQ, elucidating their potential for further studies on novel formulas of antimalarial drug regimens.

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Progenitor Cell Dynamics in Androgenetic Alopecia: Insights from Spatially Resolved Transcriptomics

Goals 3
Ensure healthy lives and promote well-being for all at all ages

Progenitor Cell Dynamics in Androgenetic Alopecia: Insights from Spatially Resolved Transcriptomics

This study examined why hair follicles shrink and thin in androgenetic alopecia (AGA), a common form of hair loss, by focusing on the decline of special hair-regenerating cells. Using advanced spatial profiling technology, we compared scalp tissue from AGA patients and healthy individuals, specifically analyzing gene activity in the regions containing these regenerative cells. We found that genes involved in scar tissue formation and cell identity changes—such as FN1, TWIST1, and TGFB2—were much more active in these areas in AGA patients. The corresponding proteins were also found at higher levels, confirming their involvement. This increased gene activity creates a harmful environment around the hair follicle, encouraging fibrosis (scar formation) and loss of regenerative cells, which likely contributes to ongoing hair thinning. Additionally, immune cells gathering near the hair follicle opening appear to influence this damaging process, suggesting that inflammation also plays a role. By identifying exactly where and how these changes occur, we highlight potential new targets for AGA treatment and advances our understanding of the underlying causes of this type of hair loss.

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