Prednosti NMNH
NMNH: 1. "Bonzyme" Celotna encimska metoda, okolju prijazna, brez škodljivih ostankov topil za proizvodnjo praška. 2. Bontac je prva proizvodnja na svetu, ki proizvaja prah NMNH na ravni visoke čistosti in stabilnosti. 3. Ekskluzivna sedemstopenjska tehnologija čiščenja "Bonpure", visoka čistost (do 99%) in stabilnost proizvodnje prahu NMNH 4. Tovarne v lastni lasti in pridobili številne mednarodne certifikate za zagotovitev visoke kakovosti in stabilne oskrbe z izdelki iz prahu NMNH 5. Zagotovite storitev prilagajanja rešitve izdelka na enem mestu
Prednosti NADH
NADH: 1. Celotna encimska metoda Bonzyme, okolju prijazna, brez škodljivih ostankov topil 2. Ekskluzivna tehnologija čiščenja v sedmih korakih Bonpure, čistost višja od 98 % 3. Posebna patentirana procesna kristalna oblika, večja stabilnost 4. Pridobil številne mednarodne certifikate za zagotovitev visoke kakovosti 5. 8 domačih in tujih patentov NADH, ki vodijo industrijo 6. Zagotovite storitev prilagajanja rešitve izdelka na enem mestu
Prednosti NAD
NAD: 1. "Bonzyme" Celotna encimska metoda, okolju prijazna, brez škodljivih ostankov topil 2. Stabilen dobavitelj 1000+ podjetij po vsem svetu 3. Edinstvena "Bonpure" sedemstopenjska tehnologija čiščenja, višja vsebnost izdelka in višja stopnja konverzije 4. Tehnologija liofilizacije za zagotovitev stabilne kakovosti izdelka 5. Edinstvena kristalna tehnologija, večja topnost izdelka 6. Tovarne v lastni lasti in pridobljene številne mednarodne certifikate za zagotavljanje visoke kakovosti in stabilne oskrbe z izdelki
Prednosti MNM
NMN: 1. "Bonzyme"Celotna encimska metoda, okolju prijazna, brez škodljivih ostankov topil 2. Ekskluzivna sedemstopenjska tehnologija čiščenja "Bonpure", visoka čistost (do 99,9%) in stabilnost 3. Vodilna industrijska tehnologija: 15 domačih in mednarodnih patentov NMN 4. Tovarne v lastni lasti in pridobljene številne mednarodne certifikate za zagotavljanje visoke kakovosti in stabilne dobave izdelkov 5. Številne študije in vivo kažejo, da je zdravilo Bontac NMN varno in učinkovito 6. Zagotovite storitev prilagajanja rešitve izdelka na enem mestu 7. Dobavitelj surovin NMN slavne ekipe Davida Sinclaira z univerze Harvard
Imamo najboljše rešitve za vaše podjetje
Bontac Bio-Engineering (Shenzhen) Co., Ltd. (hereafter referred to as BONTAC) is a high-tech enterprise established in July 2012. BONTAC integrates R&D, production and sales, with enzyme catalysis technology as the core and coenzyme and natural products as main products. There are six major series of products in BONTAC, involving coenzymes, natural products, sugar substitutes, cosmetics, dietary supplements and medical intermediates.
As the leader of the global NMN industry, BONTAC has the first whole-enzyme catalysis technology in China. Our coenzyme products are widely used in health industry, medical & beauty, green agriculture, biomedicine and other fields. BONTAC adheres to independent innovation, with more than 170 patentov za izume. Different from the traditional chemical synthesis and fermentation industry, BONTAC has advantages of green low-carbon and high-value-added biosynthesis technology. What’s more, BONTAC has established the first coenzyme engineering technology research center at the provincial level in China which also is the sole in Guangdong Province.
In the future, BONTAC will focus on its advantages of green, low-carbon and high-value-added biosynthesis technology, and build ecological relationship with academia as well as upstream/downstream partners, continuously leading the synthetic biological industry and creating a better life for human beings.
Metoda izdelave prahu NMN
NMN prah se na splošno običajno proizvaja s kemično ali encimsko sintezo ali fermentacijsko biosintezo. Obstajajo prednosti in slabosti vseh treh metod.
Chemical synthesis is expensive and labor intensive, and all raw ingredients used are categorized as “unnatural,” i.e., not from biological systems. There are, however, some advantages from the manufacturer’s perspective. The yield is well suited to mass NMN powder production, and all of those unnatural raw ingredients can be carefully controlled. But there are a number of drawbacks as well. Some of the solvents used in the manufacturing process are seriously bad from an environmental standpoint, and impurities and by-products can be challenging to remove from the finished product – that’s seriously bad for the consumer.
Enzymatic production of NMN powder, on the other hand, is considered a “green preparation method.” Like the chemical route, it’s pricey, but it offers a higher yield and impressively high purity. The finished NMN ticks all the boxes – stable, easily absorbed, lightweight, low density, and a low molecular structure.
Fermentacija je bila raziskovana tudi kot metoda proizvodnje NMN, vendar je donos, čeprav visoke kakovosti, precej breznaden, zato številna podjetja za prehranske dodatke precej razumno iščejo druge, učinkovitejše procese.
Učinkovitost NMN praška v zdravju
NMN was only considered as a source of cellular energy and an intermediate in NAD+ biosynthesis, currently, the attention of the scientific community has been paid on anti-aging activity and a variety of health benefits and pharmacological activities of NMN which are related to the restoring of NAD+. Thus, NMN has therapeutic effects towards a range of diseases, including age-induced type 2 diabetes, obesity, cerebral and cardiac ischemia, heart failure and cardiomyopathies, Alzheimer’s disease and other neurodegenerative disorders, corneal injury, macular degeneration and retinal degeneration, acute kidney injury and alcoholic liver disease.
Lastnosti in prednosti izdelka BONTAC NMN
1、“Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder
2、Exclusive“Bonpure”seven-step purification technology, high purity（up to 99.9%) and stability of production of NMN powder
3 、 Vodilna industrijska tehnologija: 15 domačih in mednarodnih patentov NMN
4 、 Tovarne v lastni lasti in pridobili številne mednarodne certifikate za zagotovitev visoke kakovosti in stabilne oskrbe z izdelki iz prahu NMN
5、Več študij in vivo kaže, da je prašek Bontac NMN varen in učinkovit
6 、 Zagotovite storitev prilagajanja rešitev izdelka na enem mestu
7 、Dobavitelj surovin NMN slavne ekipe Davida Sinclaira z univerze Harvard.
Ocene uporabnikov
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Pogosto zastavljena vprašanja
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Staranje, kot naravni proces, je ugotovljeno z zmanjšanjem proizvodnje energije v mitohondrijih različnih organov, kot so možgani, maščobno tkivo, koža, jetra, skeletne mišice in trebušna slinavka zaradi izčrpanosti NAD +. Ravni NAD + v telesu se zmanjšajo kot posledica povečanja uporabe encimov NAD + med staranjem Obstajajo tri različne poti biosinteze za proizvodnjo NAD + v celicah sesalcev, vključno z de novo sintezo iz triptofana, soli in Preiss-Handlerjeve poti. Med temi tremi potmi je NMN medprodukt, ki je vključen v biosintezo NAD + prek soli in Preiss-Handlerjeve poti. Reševalna pot je najučinkovitejša in glavna pot za biosintezo NAD +, pri kateri se nikotinamid in 5-fosforibozil-1-pirofosfat pretvorita v NMN z encimom NAMPT, čemur sledi konjugacija v ATP in pretvorba v NAD z NMNAT. Poleg tega so encimi, ki porabljajo NAD +, odgovorni za razgradnjo NAD + in posledično nastanek nikotinamida kot stranskega proizvoda.
Varnosti praška NMN ni mogoče oceniti, ker zahtevane klinične in toksikološke študije še niso bile zaključene, da bi določili priporočene varne ravni za dolgotrajno uporabo. Kljub temu sta njihova varnost in učinkovitost negotovi in nezanesljivi, saj večina od njih ni bila podvržena strogim znanstvenim predkliničnim in kliničnim testiranjem. To vprašanje se je pojavilo, ker se proizvajalci obotavljajo plačati za raziskave in klinična preskušanja zaradi potencialno nižje stopnje dobička, in ni odobritvene agencije, ki bi urejala izdelke NMN, ker je to pogosto izdelek, ki se prodaja kot funkcionalna hrana kot močno regulirano terapevtsko zdravilo. Zato so skupine za zagovorništvo potrošnikov zahtevale strožji postopek odobritve, ki od regulativnih agencij zahtevajo, da določijo standarde in omejitve za trženje zdravstvenih izdelkov proti staranju, upoštevajoč varnost, zdravje in dobro počutje N rdečih potrošnikov. zdravilo za starejše, saj lahko povečanje ravni NAD, kadar ni potrebno, povzroči nekatere škodljive učinke. Zato je treba odmerek in pogostost dopolnjevanja NMN skrbno predpisati, odvisno od vrste pomanjkanja, povezanega s starostjo, in vseh drugih zdravstvenih stanj ljudi. Druge predhodne sestavine NAD so bile raziskane za različne pomanjkljivosti, povezane s starostjo, in se uporabljajo za določene pomanjkljivosti, šele potem, ko je dokazana njihova učinkovitost in varna uporaba. Zato je treba enako načelo uporabiti tudi za NMN
Najprej preglejte tovarno. Po nekaj pregledih je NMN sodeloval, da potrošniki, ki neposredno soočijo, posvečajo več pozornosti gradnji blagovne znamke. Zato je za dobro blagovno znamko najpomembnejša kakovost, prva stvar za nadzor kakovosti surovin pa je pregled tovarne. Podjetje Bontac dejansko proizvaja NMN prah visoke kakovosti s katerijami SGS. Drugič, preizkušena je čistost. Čistost je eden najpomembnejših parametrov prahu NMN. Če NMN visoke čistosti ni mogoče zagotoviti, bodo preostale snovi verjetno presegle ustrezne standarde. Kot je razvidno iz priloženih potrdil, prah NMN, ki ga proizvaja zdravilo Bontac, doseže čistost 99,9 %. Končno je za dokazovanje potreben strokovni testni spekter. Magnetna resonančna spektroskopija (NMR) in masna spektrometrija visoke ločljivosti (HRMS). Običajno se z analizo teh dveh spektrov predhodno določi struktura spojine can.
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Najnovejše raziskave dokazujejo: Koencim NAD + lahko poveča tumorsko imunost! Strokovni komentar Kitajske akademije znanosti
On August 10, 2021, researchers from Shanghai University of Science and Technology published an article titled NAD+ supplement potentiates tumor killing function by rescuing defective TUBBY-mediated NAMPT transcription in tumor infiltrated T cells in Cell Reports, revealing that NAD+ in supplemented during CAR-T therapy and immune checkpoint inhibitor therapy, it can improve the anti-tumor activity of T. At present, the supplementary precursor of NAD+, as a nutritional product,has been verified for human consumption safety.This achievement provides a simply and feasible new method for improving the anti-tumor activity of T cells. Cancer immunotherapies including the adoptive transfer of naturally occurring tumor-infiltrating lymphocytes (TILs) and genetically engineered T cells, as well as the use of immune checkpoint blockade (ICB) to boost the function of T cells, have emerged as promising approaches to achieve durable clinical responses of otherwise treatment-refractory cancers (Lee et al., 2015; Rosenberg and Restifo, 2015; Sharma and Allison, 2015). Although immunotherapies have been successfully used in the clinic, the number of patients benefiting from them is still limited (Fradet et al., 2019; Newick et al., 2017). Tumor microenvironment (TME)-related immunosuppression has emerged as the major reason for low and/or no response to both immunotherapies (Ninomiya et al., 2015; Schoenfeld and Hellmann, 2020). Therefore, efforts to investigate and overcome TME-related limitations in immune therapies are of great urgency. The fact that immune cells and cancer cells share many fundamental metabolic pathways implies an irreconcilable competition for nutrients in TME (Andrejeva and Rathmell, 2017; Chang et al., 2015). During uncontrolled proliferation, cancer cells hijack alternative pathways for more rapid metabolite generation (Vander Heiden et al., 2009). As a consequence, nutrient depletion, hypoxia, acidity, and generation of metabolites that can be toxic in the TME may hinder successful immunotherapy (Weinberg et al., 2010). Indeed, TILs often experience mitochondrial stress within growing tumors and become exhausted (Scharping et al., 2016). Interestingly, multiple studies also indicate that metabolic changes in TME could re-shape T cell differentiation and functional activity (Bailis et al., 2019; Chang et al., 2013; Peng et al., 2016). All these evidences inspired us to hypothesize that metabolic reprogramming in T cells might rescue them from a stressed metabolic environment, thereby reinvigorating their anti-tumor activity (Buck et al., 2016; Zhang et al., 2017). In this current study, by integrating both genetic and chemical screens, we identified that NAMPT, a key gene involved in NAD+ biosynthesis, was essential for T cell activation. NAMPT inhibition led to robust NAD+ decline in T cells, thereby disrupting glycolysis regulation and mitochondrial function, blocking ATP synthesis, and dampening the T cell receptor (TCR) downstream signaling cascade. Building on the observation that TILs have relatively lower NAD+ and NAMPT expression levels than T cells from peripheral blood mononuclear cells (PBMCs) in ovarian cancer patients, we performed genetic screening in T cells and identified that Tubby (TUB) is a transcription factor for NAMPT. Finally, we applied this basic knowledge in the (pre) clinic and showed very strong evidence that supplementation with NAD+ dramatically improves the anti-tumor killing activity both in adoptively transferred CAR-T cells therapy and immune check point blockade therapy, indicating their promising potential for targeting NAD+ metabolism to better treat cancers. 1.NAD+ regulates the activation of T cells by affecting energy metabolism After antigen stimulation, T cells undergo metabolic reprogramming, from mitochondrial oxidation to glycolysis as the main source of ATP. While maintaining sufficient mitochondrial functions to support cell proliferation and effector functions.Given that NAD+ is the main coenzyme for redox, the researchers verified the effect of NAD+ on the level of metabolism in T cells through experiments such as metabolic mass spectrometry and isotope labeling. The results of in vitro experiments show that NAD+ deficiency will significantly reduce the level of glycolysis, TCA cycle and electron transport chain metabolism in T cells. Through the experiment of replenishing ATP, the researchers found that the lack of NAD+ mainly inhibits the production of ATP in T cells, thereby reducing the level of T cell activation. 2.The NAD+ salvage synthesis pathway regulated by NAMPT is essential for T cell activation The metabolic reprogramming process regulates the activation and differentiation of immune cells. Targeting T cell metabolism provides an opportunity to modulate the immune response in a cellular way. Immune cells in the tumor microenvironment, their own metabolic level will also be correspondingly affected. The researchers in this article have discovered the important role of NAMPT in the activation of T cells through genome-wide sgRNA screening and metabolism-related small molecule inhibitor screening experiments. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme for redox reactions and can be synthesized through the salvage pathway, de novo synthesis pathway, and Preiss-Handler pathway. The NAMPT metabolic enzyme is mainly involved in the NAD+ salvage synthesis pathway. Analysis of clinical tumor samples found that in tumor-infiltrating T cells, their NAD+ levels and NAMPT levels were lower than other T cells. Researchers speculate that NAD+ levels may be one of the factors that affect the anti-tumor activity of tumor-infiltrating T cells. 3.Supplement NAD+ to enhance the anti-tumor activity of T cells Immunotherapy has been exploratory research in cancer treatment, but the main problem is the best treatment strategy and the effectiveness of immunotherapy in the overall population. Researchers want to study whether enhancing the activation ability of T cells by supplementing NAD+ levels can enhance the effect of T cell-based immunotherapy. At the same time, in the anti-CD19 CAR-T therapy model and anti-PD-1 immune checkpoint inhibitor therapy model, it was verified that supplementation of NAD+ significantly enhanced the tumor-killing effect of T cells. The researchers found that in the anti-CD19 CAR-T treatment model, almost all mice in the CAR-T treatment group supplemented with NAD+ achieved tumor clearance, while the CAR-T treatment group without NAD+ supplemented only about 20 % Of mice achieved tumor clearance. Consistent with this, in the anti-PD-1 immune checkpoint inhibitor treatment model, B16F10 tumors are relatively tolerant to anti-PD-1 treatment, and the inhibitory effect is not significant. However, the growth of B16F10 tumors in the anti-PD-1 and NAD+ treatment group could be significantly inhibited. Based on this, NAD+ supplementation can enhance the anti-tumor effect of T cell-based immunotherapy. 4.How to supplement NAD+ The NAD+ molecule is large and cannot be directly absorbed and utilized by the human body. The NAD+ directly ingested orally is mainly hydrolyzed by brush border cells in the small intestine. In terms of thinking, there is indeed another way to supplement NAD+, which is to find a way to supplement a certain substance so that it can synthesize NAD+ autonomously in the human body. There are three ways to synthesize NAD+ in the human body: Preiss-Handler pathway, de novo synthesis pathway and salvage synthesis pathway. Although the three ways can synthesize NAD+, there is also a primary and secondary distinction. Among them, the NAD+ produced by the first two synthetic pathways only accounts for about 15% of the total human NAD+, and the remaining 85% is achieved through the way of remedial synthesis. In other words, the salvage synthesis pathway is the key to the human body to supplement NAD+. Among the precursors of NAD+, nicotinamide (NAM), NMN and nicotinamide ribose (NR) all synthesize NAD+ through a salvage synthesis pathway, so these three substances have become the body's choice for supplementing NAD+. Although NR itself has no side effects, in the process of NAD+ synthesis, most of it is not directly converted into NMN, but needs to be digested into NAM first, and then participate in the synthesis of NMN, which still cannot escape the limitation of rate-limiting enzymes. Therefore, the ability to supplement NAD+ through oral administration of NR is also limited . As a precursor for supplementing NAD+, NMN not only bypasses the restriction of rate-limiting enzymes, but is also absorbed very quickly in the body and can be directly converted into NAD+. Therefore, it can be used as a direct, rapid and effective method to supplement NAD+. Expert Reviews: Xu Chenqi (Excellence and Innovation Center of Molecular Cell Science, Chinese Academy of Sciences, Immunology Research Expert) Cancer treatment is a problem in the world. The development of immunotherapy has made up for the limitations of traditional cancer treatment and expanded the treatment methods of doctors. Cancer immunotherapy can be divided into immune checkpoint blocking therapy, engineered T cell therapy, tumor vaccine, etc. These treatment methods have played a certain role in the clinical treatment of cancer. At the same time, this also makes the current focus of immunotherapy research on how to further enhance the effect of immunotherapy and expand the beneficiaries of immunotherapy.
Prilagajanje prilagojenih režimov odmerjanja NMN na podlagi koncentracije NAD
Uvod Nikotinamid mononukleotid (NMN), eden od predhodnikov nikotinamid adenin dinukleotida (NAD +), je bil vpleten v več bioloških procesov, kot so celična redoks regulacija in metabolizem ter popravilo DNA. Pri tem se izvede post-hoc analiza dvojno slepega kliničnega preskušanja. Na predpostavki varnosti, da bi optimizirali uporabo NMN, se lahko razvije prilagojen režim odmerjanja s spremljanjem koncentracije NAD. Raziskovalni protokol Skupno 80 zdravih odraslih srednjih let (starost: 40 do 65 let) je vključenih v randomizirano, dvojno slepo, nadzorovano klinično preskušanje dodatkov NMN, ki so naključno razporejeni v štiri skupine in dajejo placebo ali NMN (300 mg, 600 mg ali 900 mg) 60 dni. Klinični podatki, vključno s starostjo, spolom, indeksom telesne mase (ITM), biološko starostjo krvi, oceno homeostatskega modela za odpornost na inzulin (HOMA-IR), koncentracijo NAD v krvi, 6-minutnim testom hoje in 36-točkovno kratko raziskavo (SF-36), skupaj z neželenimi učinki, se zbirajo na začetku in po dopolnitvi, čemur sledi primerjava in korelacijska analiza. Povezava kliničnih podatkov udeležencev ob izhodišču in po dopolnitvi NMN Sprememba koncentracije NAD (NADΔ) je odvisna od odmerka povečana po dodatku NMN, z velikim koeficientom variacije (29,2–113,3%) znotraj skupine. Predvsem ima samo HOMA-IR izrazito povezavo z izhodiščno vrednostjo NAD v krvi. Kot celota ima dodatek NMN pozitiven vpliv na fizično vzdržljivost in splošno zdravstveno stanje zdravih odraslih, kar dokazuje očitno izboljšanje šestminutne hoje, biološke starosti krvi in rezultata SF-36. Poleg tega je povečanje NADΔ za približno 15 nmol / L povezano s kliničnimi izboljšavami razdalje hoje 6-minutnega testa hoje in rezultatom SF-36. Varnost peroralnega odmerka NMN v kliničnih preskušanjih Kot so pokazali registrirani klinični preskušanji NCT04823260 in CTRI/2021/03/032421, lahko dodatek NMN poveča koncentracijo NAD v krvi, ki je varna in dobro prenaša z vsakodnevno peroralno uporabo 900 mg. Presenetljivo je, da klinična učinkovitost, izražena s koncentracijo NAD v krvi in fizično zmogljivostjo, doseže najvišjo pri odmerku 600 mg na dan peroralnega vnosa. Sklep Koncentracija NAD v krvi se poveča z dodatkom NMN na način, odvisen od odmerka. Prilagojeni režim dodatka NMN mora temeljiti na natančnem spremljanju spremembe koncentracije NAD. Poleg daljšega trajanja spremljanja in velike velikosti vzorca bi morala prihodnja preskušanja učinkovitosti dodatka NMN veliko pozornosti nameniti dejavnikom, ki vplivajo na izhodiščno koncentracijo NAD. Referenčni [1] Kuerec AH, Wang W, Yi L, et al. Za personalizirano dopolnitev nikotinamid mononukleotida (NMN): koncentracija nikotinamid adenin dinukleotida (NAD). Staranje mechov Dev. 2024;218:111917. doi:10.1016/j.mad.2024.111917 [2] Pesem Q, Zhou X, Xu K, Liu S, Zhu X, Yang J. Varnost in učinki proti staranju nikotinamidnega mononukleotida v kliničnih preskušanjih pri ljudeh: posodobitev. Adv Nutr. 2023; 14(6):1416-1435. doi:10.1016/j.advnut.2023.08.008 BONTAC NMN Kot je v intervjuju poudaril David Sinclair, slavni profesor genetike na univerzi Harvard, ima NMN nestabilno molekularno strukturo, ki se zlahka razgradi v nikotinamid, če je shranjena v konvencionalnem okolju. Zadovoljive učinkovitosti NMN ni mogoče zagotoviti, če kakovost in čistost izdelkov NMN nista visoki. BONTAC je prva izbira dobaviteljev surovin NMN po vsem svetu, ki se že 12 let posveča proizvodnji surovin za encime in naravne izdelke, z lastno tovarno, 173 patenti in strokovno ekipo za raziskave in razvoj. Čistost BONTAC NMN lahko doseže do 99,5%. Prav tako je BONTAC dobavitelj surovin NMN ekipe Davida Sinclaira, ki uporablja surovine BONTAC v članku z naslovom "Okvara endotelijske signalne mreže NAD + -H2S je reverzibilni vzrok vaskularnega staranja". Naše storitve in izdelki so bili visoko priznani s strani globalnih partnerjev. Koencimski izdelki BONTAC se pogosto uporabljajo na področjih, kot so prehransko zdravje, biomedicina, medicinska lepota, vsakodnevne kemikalije in zeleno kmetijstvo. Disclaimer Ta članek temelji na referenci v akademski reviji. Ustrezne informacije so na voljo samo za namene izmenjave in učenja in ne predstavljajo nobenih medicinskih nasvetov. Če pride do kršitve, se za izbris obrnite na avtorja. Stališča, izražena v tem članku, ne predstavljajo stališča skupine BONTAC. BONTAC v nobenem primeru ne bo odgovoren za kakršne koli zahtevke, škodo, izgube, izdatke, stroške ali obveznosti (vključno z, brez omejitev, kakršno koli neposredno ali posredno škodo zaradi izgube dobička, prekinitve poslovanja ali izgube informacij), ki izhajajo ali izhajajo neposredno ali posredno iz vašega zanašanja na informacije in gradivo na tej spletni strani.
NR as a Promising Therapeutic Candidate for Alpers' Disease
Introduction Alpers' disease is both a neurodegenerative disorder and a metabolic disorder, which is tightly linked to mitochondrial dysfunction and mutations in the catalytic subunit of polymerase gamma (POLG) gene. Noteworthily, supplementation of NAD precursor, nicotinamide riboside (NR), is evidenced to explicitly ameliorate mitochondrial defects in cortical organoids of patients with Alpers' disease. About Alpers’ disease Alpers’ disease is an autosomal recessive disorder, which is often accompanied with cortical neuronal loss as well as depletion of mitochondrial DNA (mtDNA) and complex I (CI). The disease occurs in about 1 in 100,000 newborns. Most individuals with Alpers’ disease show no symptoms at birth. Diagnosis is generally established by determining the POLG gene. Once onset (usually between first and third years of life), patients may present the symptoms such as progressive encephalopathy, epilepsy, myoclonus, and myasthenia gravis. Currently, there is no effective method to cure this disease. Establishment of Alpers' disease model in vitro Induced pluripotent stem cells (iPSCs) are generated from Alpers' patient carrying the compound heterozygous mutations of A467T (c.1399G>A) and P589L (c.1766C>T), followed by differentiation into cortical organoids and neural stem cells (NSCs). Alpers's iPSCs exhibit mild mitochondrial alterations, including an elevated L-lactate level and a depletion of CI. Alpers' NSCs manifest profound mtDNA depletion and mitochondrial dysfunction. Alpers' cortical organoids demonstrate cortical neuronal loss and astrocyte accumulation. The role of NR in Alpers' cortical organoids Long-term treatment with NR partially ameliorates the neurodegenerative alterations observed in Alpers' cortical organoids. Specifically, supplementation of NR effectively counteracts neuronal loss, glial enrichment, and mitochondrial damage observed in cortical organoids of patients with Alpers' disease. Reversal of the dysregulated pathways in Alpers' patient organoids post NR treatment NR treatment offsets the downregulation of mitochondrial and synaptogenesis-related pathways, as well as upregulation of pathways associated with astrocyte/glial cells and neuroinflammation are obviously activated in Alpers' cortical organoids. Conclusion Replenishment of NR to increase NAD level can rescue mitochondrial defects and neuronal loss in iPSC-derived cortical organoid of Alpers’ disease, with relatively high safety and bioavailability, showing great promise as a therapeutic candidate for this intractable disorder. Reference Hong Y, Zhang Z, Yangzom T, et al. The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC derived Cortical Organoid of Alpers' Disease. Int J Biol Sci. 2024;20(4):1194-1217. Published 2024 Jan 25. doi:10.7150/ijbs.91624 BONTAC NR BONTAC is one of the few suppliers in China that can launch mass production of raw materials for NR, with self-owned factory and professional R&D team. Up till now, there are 173 BONTAC patents. BONTAC provides one-stop service for customized products. Both malate and chloride salt forms of NR are available. By dirt of unique Bonpure seven-step purification technology and Bonzyme Whole-enzymatic method, the product content and conversion rate can be maintained in a higher level. The purity of BONTAC NR can reach above 97%. Our products are subjected to strict third-party self-inspection, which are worth of trustworthy. Disclaimer This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The opinions expressed in this article do not represent the position of BONTAC. Under no circumstances will BONTAC be held responsible or liable in any way for any claims, damages, losses, expenses, costs or liabilities whatsoever (including, without limitation, any direct or indirect damages for loss of profits, business interruption or loss of information) resulting or arising directly or indirectly from your reliance on the information and material on this website.