Punicic Acid Thiab Nws Lub Luag Haujlwm Hauv Kev Tiv Thaiv Cov Kab Mob Neurological: Kev Ntsuam Xyuas Ntu 1

Abstract:

Ntau lab tus tib neeg thoob ntiaj teb raug cuam tshuam los ntawm cov kab mob neurodegenerative (NDs). NDs muaj tus cwj pwm los ntawm kev puas tsuaj loj zuj zus thiab kev tuag ntawm cov paj hlwb nrog rau qib siab ntawm cov kab mob biomarkers thiab oxidative kev nyuaj siab.

Cov kab mob neurodegenerative, xws li Alzheimer's disease thiab dementia, yog cov kab mob uas peb ntsib niaj hnub no. Cov kab mob no yuav ua rau neuron tuag thiab hlwb hlwb atrophy nyob rau hauv tus neeg mob lub hlwb, ua rau kev txawj ntse poob. Nco yog ib qho ntawm cov chaw cuam tshuam loj tshaj plaws.

Txawm li cas los xij, txawm tias nyob rau hauv lub ntsej muag ntawm cov kab mob no, peb yuav tsum tsis txhob tso tseg kev nqis peev thiab ua haujlwm ntawm peb lub hlwb. Kev tshawb fawb qhia tau hais tias kev ua neej nyob, kev noj qab haus huv ntawm lub hlwb, thiab kev txawj ntse tuaj yeem ncua kev loj hlob ntawm cov kab mob neurodegenerative mus rau qhov loj thiab ua kom nco tau zoo.

Piv txwv li, aerobic ce thiab kev cob qhia lub hlwb tuaj yeem txhim kho lub hlwb thiab ua haujlwm thiab ncua kev paub txog kev ua haujlwm tsis zoo. Kev noj zaub mov kom zoo, noj zaub mov kom zoo, pw tsaug zog txaus, thiab kev sib raug zoo hauv zej zog kuj tseem ceeb hauv kev tswj hwm kev noj qab haus huv thiab tuaj yeem pab tiv thaiv kab mob neurodegenerative thiab khaws cia nco.

Lwm cov kws tshawb fawb ntseeg tias kev ua tau zoo ntawm tus kheej thiab kev xav sib npaug tuaj yeem pab peb khaws peb lub cim xeeb. Piv txwv li, pom peb tus kheej daws teeb meem lossis ua tiav ib lub hom phiaj ua rau peb muaj kev ntseeg siab thiab zoo siab, thiab cov kev xav no tuaj yeem pab peb tswj peb lub hlwb, uas ua rau peb nco qab zoo.

Hauv lub neej niaj hnub, peb tuaj yeem ua qee qhov kev cob qhia yooj yim los pab txhim kho kev nco. Piv txwv li: nco ntsoov cov xov tooj, hnub yug, npe, thiab lwm yam ntaub ntawv, nyeem cov lus nrov nrov, thiab rov nco qab cov ntsiab lus yog txhua txoj hauv kev zoo heev.

Txawm hais tias tus kab mob neurodegenerative yog ib yam kab mob loj, nws tseem ceeb toom rau peb kom ua neej nyob zoo thiab coj tus cwj pwm zoo kom peb lub hlwb noj qab haus huv thiab nco, thiab ua kom peb lub neej noj qab nyob zoo, ua kom tiav, thiab zoo dua! Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj hauv Suav teb uas muaj ntau yam teebmeem, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm Cistanche deserticola los ntawm ntau yam khoom xyaw uas nws muaj, suav nrog tannic acid, polysaccharides, flavonoid glycosides, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv los ntawm ntau txoj hauv kev.

Nyem Paub Short-term Nco yuav ua li cas txhim kho

Punicic acid, lub ntsiab bioactive tivthaiv ntawm pomegranate (Punica granatum) noob roj, yog ib tug omega -5 isomer ntawm conjugated -linoleic acid uas tau pom muaj zog los tiv thaiv oxidative thiab anti-inflammatory teebmeem uas ua rau nws muaj txiaj ntsig zoo tiv thaiv ntau yam ntawm kab mob. Punicic acid txo oxidative kev puas tsuaj thiab o los ntawm kev nthuav qhia ntawm peroxisome proliferator-activated receptors.

Tsis tas li ntawd, nws tuaj yeem txo qis beta-amyloid deposit tsim thiab tau hyperphosphorylation los ntawm kev nce qhov kev qhia ntawm GLUT4 protein thiab inhibition ntawm calpain hyperactivation. Microencapsulated pomegranate, nrog rau qib siab ntawm punicic acid, nce antioxidant PON1 kev ua haujlwm hauv HDL. Ib yam li ntawd, encapsulatedpomegranate formulations nrog cov qib siab ntawm punicic acid tau pom tias muaj kev nce hauv antioxidantPON1 kev ua hauv HDL.

Vim hais tias ntawm lub hlwb tsis muaj permeability ntawm punicic acid, ntau yam kev xa tawm tau tsim los txhim kho kev ua haujlwm lom neeg ntawm punicic acid hauv lub hlwb, txo qis cov tsos mob ntawm cov kab mob neurological.

Punicic acid yog ib qho tseem ceeb nutraceutical compound hauv kev tiv thaiv thiab kho cov kab mob neurodegenerative xws li Alzheimer's, Parkinson's, thiab Huntington's disease.

Ntsiab lus: antioxidant; conjugated linoleic acid; ntshav-hlwb barrier; Alzheimer tus kab mob; Tus kab mob Parkinson; Huntington tus kab mob; neurodegeneration.

1. Taw qhia

Qee cov kab mob uas muaj ntau tshaj plaws uas tuaj yeem ua rau tsis muaj kev ywj pheej hauv cov neeg laus yog cov kab mob neurodegenerative (NDs), uas tau dhau los ua ntau zaus.Cov txheej txheem neurodegenerative yog qhov kev loj hlob ntawm kev ua haujlwm lossis kev tuag ntawm cov hlwb hauv nruab nrab, ua rau muaj kev nce hauv lub cev thiab kev txawj ntse. kev puas tsuaj nrog lub sijhawm [1].

Ntawm cov NDs ntau tshaj plaws yog Alzheimer's Disease (AD) thiab frontotemporal dementia, Parkinson's Disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS), thiab ntau yam spinocerebellar ataxias. Kev tshwm sim AD hauv cov pej xeem hnub nyoog 85 xyoos thiab overis txog 30%, thaum PD yog nyob ib ncig ntawm 2% ntawm cov neeg laus dua 65 xyoo, thiab ALS tau tshaj tawm txog 1-2 tus neeg rau 100,000 cov neeg ib xyoos ib zaug, thiab qhov xwm txheej yuav tsum nce siab. raws li cov pejxeem [2].

Yog li ntawd, yuav tsum muaj kev siv cov kev tiv thaiv tshiab thiab kev tsim kho tshiab rau cov theem pib ntawm neurodegeneration. Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv (WorldHealth Organization) kwv yees tias lub ntiaj teb kev sib raug zoo ntawm tus nqi dementia yog $ 818 billion, sib npaug rau 1.1% ntawm cov khoom lag luam hauv ntiaj teb. Kev nthuav dav ntawm AD hauv LatinAmerica yog siab li 8.5%.

Ntxiv mus, nws xav tias los ntawm 2030 txog 65.7 lab yuav nyob nrog dementia thiab nyob ib ncig ntawm 115.4 lab los ntawm 2050 [3]. Kev tuag thiab tib neeg kev xiam oob khab los ntawm cov kab mob neurological no tau nce ntxiv, vim li no, suav tias yog kev sib tw kev noj qab haus huv thoob ntiaj teb. Raws li qhov xwm txheej yuav tsum tau nce siab raws li cov pej xeem, nrhiav cov kev daws teeb meem tshiab thiab cov tswv yim rau kev kho cov kab mob neurodegenerative yog lub hom phiaj ntawm kev ceev nrawm. Vim hais tias oxidative puas thiab o yog keypathways nyob rau hauv txoj kev loj hlob ntawm neurodegeneration, phytochemicals nrog elevated antioxidative thiab anti-inflammatory zog yog raug soj ntsuam los pab nyob rau hauv kev tiv thaiv ntawm neurodegeneration thiab halt kab mob.

Pomegranate (Punica granatum) yog cov txiv hmab txiv ntoo qub thiab hloov tau los ntawm WesternAsia uas yog tsev neeg Punicaceae. Nws tau cog qoob loo thoob plaws ntiaj teb, suav nrog Middle Eastern, Neeg Esxias, European, thiab Asmeskas lub tebchaws, feem ntau hauv thaj chaw sov sov thiab kub kub nyob rau hauv cov xwm txheej hloov pauv huab cua [4,5]. Kwv yees li 50% ntawm tag nrho qhov hnyav ntawm cov txiv hmab txiv ntoo sib raug rau lub tev, uas yog ib qho tseem ceeb ntawm phenolic compounds, minerals, thiab complex polysaccharides. Lub caij no, qhov noj tau ntawm pomegranatefruit muaj arils (40%) nplua nuj nyob rau hauv dej, suab thaj, pectin, thiab noob (10%) [6].

Pomegranateseeds muaj ntau yam xws li polyphenols thiab fatty acids uas ua rau lawv cov txiaj ntsig zoo. Pomegranate Seed Oil (PSO) sawv cev ib ncig ntawm 12% thiab 20% ntawm tag nrho cov noob hnyav [7]. PSO muaj 14 fatty acids, ntau tshaj ntawm cov uas yog punicic acid5{18}}-8{{20}}% [7–9], ua raws li linoleic acid (13-20%), palmitic acid (6-9%), stearic acid (2-3%), oleic acid (8-9%), linolenic acid (0.06-0.08%), thiab arachidic acid (0.68-0.90%) [9].

Punicic acid, PSO lub ntsiab bioactive tivthaiv, tau pom tias ua kom muaj zog tiv thaiv oxidativeeffect uas ua rau nws cov txiaj ntsig zoo tiv thaiv ntau yam kab mob xws li pob txha, muaj zog tiv thaiv kev rog, nce kev qhia ntawm antioxidant thiab lipid metabolism ntsig txog cov noob, thiab hloov cov muaj pes tsawg leeg thiab kev ua haujlwm ntawm high-densitylipoprotein (HDL) [10–13].

Punicic acid yog omega -5 isomer ntawm conjugated -linolenic acid (CLnA) thiab nthuav tawm cov qauv zoo sib xws rau conjugated linoleic acid (CLA) [12]. Los ntawm nws tus kheej, punicic acid muaj qhov dav dav ntawm cov tshuaj lom neeg xws li tshuaj tiv thaiv kab mob, tiv thaiv kab mob ntshav qab zib, tiv thaiv rog, tiv thaiv kev loj hlob, thiab tiv thaiv kab mob carcinogenic [14,15]. Lub ntsiab ntawm cov txheej txheem lom neeg uas tau piav qhia rau punicic acid suav nrog kev hloov pauv ntawm qhov sib txawv ntawm peroxisome proliferator-activated receptors (PPARs), uas tswj cov kev qhia ntawm cov noob koom nrog hauv kev sib txawv ntawm tes thiab kev loj hlob, tswj cov enzymes koom nrog hauv lipidsmetabolism, thiab qabzib homeostasis.

Tsis tas li ntawd, PPARs muaj feem cuam tshuam nrog kev ua kom thiab tsim cov tshuaj tiv thaiv biomarkers [16–19]. Thaum cov tshuaj tiv thaiv antioxidant thiab tiv thaiv kab mob ntawm punicic acid tuaj yeem muab cov txiaj ntsig zoo ntawm kev kho mob ntawm NDs, txoj kev nws cuam tshuam rau ntau txoj hauv kev uas cuam tshuam nrog kev nce qib ntawm NDs tuaj yeem muab nws zoo dua lwm cov tshuaj tiv thaiv oxidative nutraceuticals.

Qhov kev tshuaj xyuas no tsom mus rau cov ntsiab lus ntawm cov kev paub tam sim no txog cov txiaj ntsig zoo ntawm punicic acidin neurological ntshawv siab thiab cov txheej txheem molecular cuam tshuam rau nws cov teebmeem.

2. Txoj hauv kev tseem ceeb cuam tshuam nrog cov kab mob Neurological

Txawm hais tias txhua tus NDs muaj cov kab mob sib txawv thiab cov tsos mob, lawv txoj hauv kev qhia qee qhov xwm txheej. Ib lub tswv yim qauv faib cov kev sib txawv uas koom nrog hauv neurodegeneration tau tsim los txiav txim siab txog plaub tus qauv loj ntawm kev ua [20](Daim duab 1).

Feem ntau, txoj hauv kev uas ua rau muaj kev muaj sia nyob ntawm neuron thiab degeneration suav nrog: (1) cov txheej txheem intracellular xws li apoptosis [21], autophagy [22], mitochondrial muaj nuj nqi, oxidative puas tsuaj, thiab kho [23], ubiquitin / proteasome [24], (2 ) ib puag ncig ib puag ncig xws li cell adhesion [25], endocytosis, neurotransmission [26], prions/transmissible factor [27], (3) ib puag ncig xws li mob / tiv thaiv kab mob [28], lipid / endocrine metabolism [29], lub hlwb vasculature [30], (4) thiab mechanisms ntsig txog kev laus [31], piv txwv li, epigenetics [32], neurotrophic yam [33], thiab telomeres [34]. Tag nrho cov khoom no muaj feem cuam tshuam thiab cuam tshuam nrog ib leeg los hloov cov txheej txheem neurodegenerative (Daim duab 2).

2.1. Intracellular Mechanism

Ntawm cov txheej txheem intracellular ntsig txog neuron ciaj sia thiab degeneration, DNAdamage thiab kho qhov tsis xws luag yog cov cim tseem ceeb tshaj plaws uas muaj ntau yam NDs nrog cov yam ntxwv ntawm kev hloov pauv hloov pauv.

Ib tug siab concentration ntawm reactive oxygen hom (ROS) yuav ua rau tsub zuj zuj ntawm oxidative DNA puas nyob rau hauv nws ib theem zuj zus thiab epigeneticmodifications [24]. Hloov cov noob qhia tuaj yeem ua rau poob ntawm ib txwm ua haujlwm neural thiab nce zuj zus ua rau kev ua haujlwm ntawm tes tuag thiab neuronal poob [22]. Mitochondria yog lub hauv paus loj ntawm cellular ROS ntau lawm, thiab nws tau pom tias oxidative puas tuaj yeem txhawb nqa -synuclein aggregation thiab cuam tshuam rau amyloid- (A) thiab lwm cov proteins uas cuam tshuam txog kev laus thiab ND [22,35].Nyob rau hauv lub neej ntev, tsis yog-mitotic hlwb xws li Raws li cov neurons, ROS abundance ua rau oxidativestress thiab impairment ntawm antioxidant tiv thaiv, uas ua rau dysfunction ntawm mitochondria thiab pib ntawm cell tuag cascade [36].

Ntau cov kev tshawb fawb cuam tshuam txog cov teebmeem ntawm nitricoxide thiab ROS nrog NDs, suav nrog nitration ntawm Lewis lub cev hauv Lewis lub cev dementia thiab Alzheimer's Disease (AD), nitration ntawm -synucleins hauv cov neeg mob uas muaj ntau lub cev atrophy, dav nitrates tau proteins hauv AD, thiab frontotemporal dementiawith Parkinsonism. Kev txo qis ntawm nitric oxide pab txhawb kev txhim kho ntawm A hauv lub paj hlwb, thiab nitric oxide inhibition ncua kev loj hlob ntawm Parkinson's Disease pathology [37].

Ib yam li ntawd, Tumor Necrosis Factor-alpha (TNF-) yog apro-inflammatory cytokine ntsig txog cov kab mob ntawm ND los ntawm kev mob plab [38]. Anti-TNF- kev kho mob tau npaj los ntawm ntau qhov kev tshawb fawb kom txo qis ADpathology, txo cov amyloid deposition, thiab txo qis kev puas hlwb neuronal [39]. Tsis tas li ntawd, lub hlwb cov tshuaj insulin kuj tau piav qhia tias yog ib qho tseem ceeb rau induce cognitive impairments thiab neurodegeneration.

Cov tshuaj insulin hauv hlwb raug txo thaum lub sijhawm laus thiab Alzheimer ua rau muaj kev cuam tshuam ntawm ntau phosphatase koom nrog Tau dephosphorylation uas ua rau muaj kev tso tawm thiab sib sau ntawm cov kab mob extracellular amyloid- (A) plaques [40,41].

Daim duab 2. Schematic sawv cev ntawm kev sib koom physiopathological cov cim nyob rau hauv neurodegenerativediseases (NDs): (1) Mitochondrial dysfunction vim oxidative kev nyuaj siab, laus, los yog vim geneticor ib puag ncig tej yam kev puas tsuaj, ua nyob rau hauv ntau ntau lawm ntawm ROS, uas muaj peev xwm activatep53 thiab Bax ( apoptotic regulator) translocation uas tso cai rau tso tawm cytochrome C (Cyt C) Daim duab 2.

Schematic sawv cev ntawm kev sib koom physiopathological cov cim hauv cov kab mob neurodegenerative (NDs): (1) Mitochondrial dysfunction vim oxidative kev nyuaj siab, kev laus, los yog vim geneticor ib puag ncig tej yam kev puas tsuaj, ua rau cov ntau lawm ntawm ROS, uas muaj peev xwm activatep53 thiab lub Bax (apoptotic regulator) translocation uas tso cai rau kev tso tawm ntawm cytochrome C (Cyt C) ua rau (Cas 9) thiab caspase 3 (Cas3) ua kom, ua rau DNA puas thiab cell tuag lossis (2) Apoptosis.

Ib yam li ntawd, ntau ROS ntau lawm kuj ua rau oxidative kev nyuaj siab thiab (3) LipidPeroxidation, uas tuaj yeem ua rau cov protein aggregates xws li -synuclein thiab misfolded amyloid peptide, tom kawg ua amyloid (A) plaque cuam tshuam rau neuron signaling induced los ntawm (4) Cholinergic Insufficiency. Nyob rau hauv lem, tsub zuj zuj ntawm A plaque induces (5) Microglia Activation nrog lub concomitant tso tawm ntawm (6) Inflammatory Cytokines thiab tsim neuroinflammation.

Ntawm qhov tod tes, (7) Dysregulation ntawm Ca2+ vim hais tias ntawm neuronal membrane depolarization tuaj yeem ua rau cov synaptic deficits thiab txhawb cov tsub zuj zuj ntawm A plaques, thiab (8) NeurofibrillaryTangles los ntawm calpain activation. Tsis tas li ntawd, kev txhawb nqa calcium inflow ua rau muaj kev ua haujlwm dhau ntawm neuronal nitric oxide synthase (nNOS), nrog rau kev nce hauv nitric oxide synthesis ua rau oxidativestress / nitrosative stress thiab generalized hlwb o. Ntxiv mus, ROS tsub zuj zuj induces (9) kinase activation (glycogen synthase kinase-3 , GSK-3 ) thiab induces tau hyperphosphorylation, txhawb cov tsub zuj zuj ntawm A plaques.

Kev sib sau ntawm A oligomers ua rau tshem tawm cov tshuaj insulin receptors (IRS) los ntawm lub xovtooj ntawm tes, inducing a (10) Neuronal Insulin Resistance thiab inhibiting the activation of glucose transporter type 4 (GLUT 4). Kev ua haujlwm tsis zoo ntawm cov tshuaj insulin ua rau lub hom phiaj tseem ceeb ntawm rapamycin (mTOR) txoj hauv kev thiab ua rau (11) Autophagy tsis ua hauj lwm kom khaws cov plaques.

Thaum kawg, cov cholesterol synthesized khi apolipoprotein E (APOE) los tsim APOE-cholesterol (APOE-CH) hais. APOE-CH particles yog internalized rau hauv neurons, thiab cov roj (cholesterol) dawb yog metabolized rau 24-hydroxycholesterol (24-OHC), uas tom qab ntawd dhau los ntawm cov ntshav-hlwb barrier (BBB) ​​thiab nkag mus rau hauv plasma, thaum plasma (12). ) 27 hydroxyl cholesterol (27-OHC) ntws mus rau hauv lub hlwb, nce qib ntawm -synuclein thiab nws thiaj li tsim Lewy lub cev (LBs). Cov kab rov qab qhia tias stimulation, thaum cov kab liab qhia inhibition.

2.2. Local Tissue Environment

Kev sib sau ua ke ntawm cov misfolded protein ntau uas cuam tshuam rau cov ntaub so ntswg hauv zos, tsim kev puas tsuaj, yog ib qho kab mob uas ua rau cov kab mob neurodegenerative [42]. Cov misfolded proteins no raug rau cov protein degradation, xws li proteasome-mediated. Inhibition ntawm cov protein degradation txoj hauv kev ua rau kev tsim cov protease-resistant, yog li, txo cov propagation ntawm cov proteins uas txhawb cov misfolding ntawm cov proteins [43].

Ib yam li ntawd, autophagy yog lub luag haujlwm tseem ceeb rau kev tshem tawm cov protein sib xyaw ua ke, ua haujlwm tsis zoo ntawm cov cellular organelles, thiab cov kab mob ua kom cov cellular homeostasis. Kev sib sau ntawm cov tsis paub qab hau autophagic vacuoles (AVs) raws li qhov tshwm sim ntawm kev cuam tshuam ntawm autophagy txheej txheem yog ib qho kev pom zoo nyob rau hauv lub hlwb ntawm Alzheimer's cov neeg mob.

Nws tau pom tias lub hom phiaj mammalian ntawm rapamycin (mTOR) cov cim qhia yog inhibited hauv cortex thiab hippocampus ntawm cov laus AD qauv nas. Braininsulin resistance induces alterations in insulin/insulin-like growth factor (IGF-1)-PI3K(phosphoinositide 3-}kinase class I)-Akt pathway, ua rau muaj qhov ua kom tsis zoo ntawm mTOR signaling, uas ua rau tsis zoo autophagy. induction [44–46].

2.3. Systemic Ib puag ncig

Cov kev hloov pauv hauv ib puag ncig xws li o tuaj yeem tshwm sim hauv cov kab mob neurodegenerative xws li AD thiab Parkinson's Disease (PD) thiab tuaj yeem ua rau, nrog rau kev nyuaj siab oxidative, cuam tshuam rau hauv cov proteome muaj pes tsawg leeg ntawm High-Density Lipoprotein (HDL) [47]. Circulating HDL muab kev tiv thaiv rau cerebrovascular dysfunction nyob rau hauv AD, uas plays lub luag hauj lwm tseem ceeb nyob rau hauv lub hlwb metabolism thiab homeostasis, dampening lub clearance ntawm A thiab tau thiab yog li ua rau tsim ntawm neuritic plaques thiab neurofibrillarytangles [48].

2.4. Aging Mechanism

Cov muaj pes tsawg leeg ntawm fatty acids thiab fluidity ntawm lub paj hlwb hloov nrog lub hnub nyoog.Polyunsaturated Fatty Acids (PUFAs) xws li docosahexaenoic acid (DHA, 22:6 n-3) andarachidonic acid (AA, 20:4 n{{5}). }) yog cov PUFAs ntau tshaj plaws thiab tseem ceeb hauv lub hlwb thiab ua lub luag haujlwm tseem ceeb hauv kev laus thiab neurodegeneration. Hauv cov neeg laus, DHA thiab AA txo qis hauv daim nyias nyias ntawm orbitofrontal cortex. DHA tshwj xeeb tsis muaj peev xwm tuaj yeem vim muaj hnub nyoog txog kev txo qis hauv kev ua haujlwm enzyme koom nrog kev tswj hwm ntawm DHAsynthesis, uptake, thiab sib dhos rau hauv hlwb phospholipids (Zhang li al., 2018).

Lub caij no, kev noj zaub mov ntau ntawm omega -3 thiab omega -6 PUFAs yog qhov zoo rau kev nco txog kev noj qab haus huv ntawm tib neeg cov laus. Cov txheej txheem no yog kho los ntawm kev ncaj ncees thiab kev khaws cia ntawm cov teeb meem dawb microstructure ntawm fornix nyob rau hauv lub hlwb (Zamroziewicz li al., 2017). Ntau PUFAs xws li DHA thiab AA tau raug kawm rau kev tsim kho tshiab ntawm NDs thiab neurodegeneration [49, 50].

Punicic acid (18: 3, ∆9cis, 11trans, 13cis, n-5) yog ib tus neeg sib tw cog lus uas nws cov txheej txheem ntawm kev txiav txim tseem tsis tau to taub tag nrho. Cov lus hauv qab no yuav hais txog cov yam ntxwv thiab cov txheej txheem ntawm kev txaus siab ntawm cov kua qaub punicic thiab lawv cov kev sib raug zoo nrog kev tiv thaiv ntawm NDs.

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