By Cocer Peptides 
kwanaki 27 da suka gabata
DUKKANIN LABARI DA BAYANIN KYAUTATAWA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da duk wani yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
Dubawa
Kamuwa da cutar kanjamau da maganin rigakafin cutar kanjamau (ART) da ke haifar da rashin lafiyar kitse na haifar da babban kalubale ga lafiya da ingancin rayuwar masu cutar kanjamau. Wadannan abubuwan rashin daidaituwa suna bayyana ta nau'i daban-daban, kamar lipoatrophy da lipohypertrophy, tare da yawan tarin visceral adipose tissue (VAT) wanda ya shahara musamman. Haɓakawa a cikin VAT ba wai kawai yana rinjayar bayyanar jiki na marasa lafiya ba amma yana da alaƙa da alaƙa da kewayon rikice-rikice na rayuwa mai tsanani, ciki har da cututtukan zuciya, juriya na insulin, da cututtukan hanta maras barasa (NAFLD), yana haifar da mummunar barazana ga rayuwa na dogon lokaci na marasa lafiya.
Tesamoreli, wani analog na haɓakar haɓakar haɓakar ƙwayar cuta (GHHRH), yana ba da sabon bege don maganin rashin lafiyar mai mai a cikin marasa lafiya na HIV. Yana ɗaure musamman ga masu karɓar GHRH a cikin glandar pituitary na gaba, yana ƙarfafa haɓakar haɓakawa da sakin hormone girma na endogenous (GH). GH yana taka muhimmiyar rawa wajen daidaita metabolism na mai a cikin jikin mutum, haɓaka lipolysis, haɓaka haɓakar acid fatty acid, da daidaita maganganun kwayoyin halittar da ke da alaƙa da metabolism na lipid, don haka yin tasiri mai kyau akan metabolism mai. Wannan tsarin aiki na musamman yana ba Tesamoreli damar taimakawa inganta rikice-rikicen metabolism na mai a cikin masu cutar HIV.
Hoto na 1 Tsarin Bincike. An bincika jimillar sunadaran sunadaran plasma guda 9, wanda ya yi daidai da manyan manyan kwayoyin halitta a cikin hanyoyin hanta da aka bambanta ta hanyar tesamorelin.
Hanyar Ayyukan Tesamoreli akan Fat Metabolism a HIV
Marasa lafiya
Ka'idar Girman Hormone-Insulin-Kamar Growth Factor Axis
Tesamoreli yana ɗaure ga mai karɓar GHRH akan membrane cell na glandan pituitary na baya, yana kunna hanyoyin sigina masu alaƙa da mai karɓa kamar hanyar siginar JAK-STAT. Wannan tsarin kunnawa yana haɓaka haɓakawa da sakin hormone girma (GH) ta glandan pituitary na gaba. Bayan shiga cikin jini, ya kai ga gabobin da aka yi niyya kamar hanta, yana motsa hanta don haɗawa da ɓoye abubuwan haɓakar insulin-kamar-1 (IGF-1). IGF-1 yana aiki a matsayin babban matsakanci na tasirin GH kuma yana taka muhimmiyar rawa a cikin metabolism mai. IGF-1 na iya kunna hanyar siginar PI3K-AKT, hana adipocyte apoptosis, da kuma kula da aikin adipocyte na yau da kullun. Har ila yau, yana inganta haɓakawa da oxidation na fatty acid ta adipocytes, yana rage yawan kitse a cikin sel. A cikin marasa lafiya na HIV, aikin haɓakar hormone-insulin-kamar girma factor axis sau da yawa yakan lalace saboda cutar kanta da kuma tasirin maganin antiretroviral (ART). Tesamoreli na iya kunna wannan axis don dawo da aikin sarrafa kitse na al'ada.
Tasirin kai tsaye akan metabolism na adipocyte
Haɓaka lipolysis: Tesamoreli na iya haɓaka magana da aiki na lipase mai jin daɗin hormone (HSL) a cikin adipocytes. HSL shine mabuɗin enzyme a cikin lipolysis, yana haɓaka hydrolysis na triglycerides cikin glycerol da fatty acid, ta haka yana haɓaka metabolism na kitse. A cikin vitro, ƙara Tesamoreli zuwa adipocytes na al'ada yana haɓaka aikin HSL sosai kuma yana haɓaka sakin fatty acid. Tesamoreli kuma yana iya kunna HSL a kaikaice ta hanyar daidaita hanyar siginar AMP (cAMP) -protein kinase A (PKA), yana ƙara haɓaka lipolysis. A cikin marasa lafiya na HIV, wannan tasirin haɓakar lipolysis yana taimakawa rage yawan kitse mai yawa, musamman raguwar kitse na visceral, don haka inganta rarraba mai mara kyau a cikin marasa lafiya.
Ka'idar oxidation fatty acid: Tesamoreli yana haɓaka ayyukan mahimman enzymes waɗanda ke cikin fatty acid oxidation a cikin adipocytes, kamar carnitine palmitoyltransferase 1 (CPT1). CPT1 shine ƙarancin ƙarancin enzyme don shigar da fatty acid shiga cikin mitochondria don β-oxidation, kuma ingantaccen aikin sa yana haɓaka rushewar oxidative na fatty acid a cikin mitochondria, yana ba da kuzari ga sel. Tesamoreli kuma na iya daidaita maganganun sauran enzymes da masu jigilar kaya da ke cikin fatty acid β-oxidation, irin su acetyl-CoA carboxylase 2 (ACC2) da fatty acid transporter 1 (FATP1), yana kara inganta tsarin metabolism na fatty acid oxidation. Ta hanyar haɓaka oxidation fatty acid, Tesamoreli na iya rage ajiyar kitse a cikin sel kuma inganta rikicewar metabolism na lipid a cikin marasa lafiya na HIV.
Ƙa'idar magana mai alaƙa da ƙwayar lipid metabolism
Tasirin kwayoyin halitta masu alaka da adipogenesis: Tesamoreli na iya hana maganganun kwayoyin halitta masu alaka da adipogenesis, irin su peroxisome proliferator-activated receptor γ (PPARγ) da CCAT / haɓaka-daurin furotin α (C / EBPa). PPARγ shine maɓalli mai mahimmanci na rubutu a cikin bambance-bambancen adipocyte da adipogenesis, yana inganta bambance-bambancen fibroblasts a cikin adipocytes balagagge, kuma yana haifar da bayyanar da jerin kwayoyin halitta masu alaka da adipogenesis, irin su fatty acid-binding protein 4 (FABP4) da fatty acid synthase (FAS). C/EBPa kuma yana taka muhimmiyar rawa a cikin bambance-bambancen adipocyte da adipogenesis. Ta hanyar hana maganganun PPARγ da C / EBPa, Tesamoreli yana rage bambance-bambancen adipocyte da adipogenesis, don haka rage yawan kitse a cikin jiki. A cikin masu cutar kanjamau, wannan sakamako na ka'ida akan kwayoyin halittar adipogenesis yana taimakawa gyara yawan kitse mai yawa wanda ke haifar da ƙarancin kitse mai yawa.
Hoto 2 Dangantakar Canje-canje a cikin Plasma VEGFA da CSF1 tare da Canji a Makin NAS a cikin Mahalarta da Tesamoreli da aka yi wa magani.
Tsarin jigilar lipid da kwayoyin halitta: Tesamoreli na iya daidaita maganganun kwayoyin halittar da ke da alaƙa da jigilar lipid da metabolism, kamar membobin dangin apolipoprotein (Apo). ApoB shine farkon apolipoprotein na lipoprotein mai ƙarancin yawa (VLDL) da ƙananan lipoprotein mai ƙarancin yawa (LDL), kuma matakan maganganun sa suna da alaƙa da matakan VLDL da LDL a cikin jini. Tesamoreli na iya rage maganganun ApoB, rage kira da ɓoyewar VLDL da LDL, don haka rage matakan plasma na lipoproteins atherogenic. Bugu da ƙari, Tesamoreli na iya daidaita maganganun ApoA-I, babban apolipoprotein na babban adadin lipoprotein (HDL). Ƙara yawan maganganun ApoA-I yana taimakawa haɓaka matakan HDL, inganta jigilar cholesterol baya, da rage haɗarin cututtukan zuciya. A cikin marasa lafiya na HIV, inda rikice-rikicen metabolism na lipid sau da yawa suna tare da rashin daidaituwa na lipid metabolism, tasirin Tesamoreli akan jigilar lipid da kwayoyin halitta na iya taimakawa inganta bayanan lipid na marasa lafiya.
Takamaiman Tasirin Tesamoreli akan Metabolism na Lipid a cikin Marasa lafiya na HIV
Rage Visceral Adipose Tissue (VAT)
Tesamoreli yana rage VAT sosai a cikin masu cutar HIV. A cikin gwaji na asibiti na Phase III wanda ya shafi marasa lafiya na HIV, an ba wa mahalarta damar karɓar ko dai 2 MG na Tesamoreli kowace rana ko placebo na makonni 26. A cikin rukunin jiyya na Tesamoreli, marasa lafiya sun nuna raguwa mai yawa a cikin VAT, kuma an lura da wannan raguwa a cikin marasa lafiya tare da halaye daban-daban na asali (misali, kasancewar ko rashin kitse na baya). Ga masu amsa Tesamoreli (wanda aka bayyana a matsayin marasa lafiya tare da aƙalla 8% raguwa a cikin VAT kuma waɗanda suka bi jiyya), VAT ya ragu sosai ba tare da la'akari da kasancewar wuyansa da kitsen baya ba, kuma babu wani bambanci mai mahimmanci tsakanin ƙungiyoyi biyu (P = 0.657). Wannan yana nuna cewa Tesamoreli yana da fa'ida mai fa'ida wajen rage VAT a cikin masu cutar kanjamau, ba tare da kasancewar kitse na baya ba. Ragewar VAT ba wai yana inganta bayyanar jikin marasa lafiya kawai ba amma mafi mahimmanci yana rage haɗarin rikice-rikicen da ke da alaƙa da VAT, kamar cututtukan zuciya da jijiyoyin jini da juriya na insulin.
Inganta hanta mai metabolism
Rage abubuwan da ke cikin hanta: A cikin marasa lafiya na HIV, abubuwan da ke faruwa na cututtukan hanta mai kitse (NAFLD) ba su da yawa kuma suna da alaƙa da haɓakar ƙwayar kitse mara kyau. Tesamoreli yana da ingantaccen tasirin warkewa akan NAFLD mai alaƙa da HIV. A cikin bazuwar, makafi biyu, binciken multicenter, marasa lafiya da ke kamuwa da cutar HIV tare da raguwar mai mai hanta (HFF) ≥5% an ba da izini ga ƙungiyar tesamorelin ko ƙungiyar placebo kuma an bi da su tsawon watanni 12. Sakamakon ya nuna cewa marasa lafiya a cikin ƙungiyar Tesamoreli sun sami raguwa mai mahimmanci a cikin HFF, tare da cikakken tasirin sakamako na -4.1% (95% CI -7.6 zuwa -0.7, P = 0.018) da raguwar dangi na 37% daga asali (95% CI -67 zuwa -7, P = 0.016). Bayan watanni 12 na jiyya, 35% na marasa lafiya a cikin rukunin Tesamoreli suna da matakan HFF da ke ƙasa da 5%, idan aka kwatanta da 4% kawai a cikin rukunin placebo (P = 0.0069). Wannan yana nuna cewa Tesamoreli yana rage yawan kitsen hanta yadda ya kamata kuma yana inganta ƙwayar hanta a cikin masu cutar HIV.
Abubuwan da za a iya yi a kan tarihin hanta: Binciken bayanan bayanan hanta a cikin marasa lafiya na HIV-NAFLD ya nuna cewa Tesamoreli ya rushe tsarin kwayoyin halitta da ke hade da kumburi, gyaran nama, da rarraba tantanin halitta a cikin hanta. Ƙarin nazarin ilimin kimiyya ya nuna cewa Tesamoreli ya haifar da raguwa mai yawa a cikin matakan furotin na plasma na ƙwayoyin cuta na endothelial girma factor A (VEGFA), canza yanayin girma β1 (TGFB1), da macrophage colony-stimulating factor 1 (CSF1), wanda ke da alaƙa da hanta fibrosis da kumburi. A cikin marasa lafiya da aka bi da Tesamoreli, raguwa a cikin plasma VEGFA da CSF1 an haɗa su tare da raguwa a cikin ayyukan NAFLD, yayin da raguwa a cikin TGFB1 da CSF1 an haɗa su tare da raguwa a cikin matakan fibrosis na jinsi. Wannan yana nuna cewa Tesamoreli na iya yin tasiri mai amfani akan tarihin hanta ta hanyar daidaita kumburi da hanyoyin da ke da alaƙa da fibrosis a cikin hanta.
Hoto 3 Dangantakar Canje-canje a cikin Plasma TGFB1 da CSF1 tare da Canji a Matsayin Fibrosis na Gene-Level a cikin Mahalarta Magance Tesamoreli.
Ka'idar Rarraba Fat ɗin Jiki Gabaɗaya da Haɗin Jiki
Rage kitsen gangar jikin: Baya ga rage VAT, Tesamoreli kuma yana da tasiri mai mahimmanci akan kitsen gangar jikin masu cutar HIV. A cikin nazarin asibiti, marasa lafiya da aka bi da su tare da Tesamoreli sun nuna raguwa a hankali a cikin abubuwan da ke cikin jikin jiki, wanda ke taimakawa wajen inganta siffar jiki da kuma rage al'amurra irin su haɓakar ciki wanda ya haifar da rarraba mai mai yawa. Rage kitsen gangar jikin yana da alaƙa da raguwar VAT, tare da haɓaka tsarin jiki.
Inganta kewayen kugu: Dawafin kugu alama ce mai mahimmanci na tarin kitsen ciki. Jiyya na Tesamoreli yana inganta kewayen kugu sosai a cikin masu cutar HIV. A cikin gwaje-gwajen asibiti masu dacewa, duka masu amsa Tesamoreli tare da kuma ba tare da kitse na baya ba sun nuna raguwa mai yawa a cikin kewayen kugu bayan makonni 26 na jiyya. Haɓakawa a cikin kewayen kugu ba wai kawai yana nuna rage kitsen ciki ba amma yana da alaƙa da alaƙa da rage haɗarin rayuwa kamar cututtukan zuciya.
Tasiri akan wasu sigogin abun da ke cikin jiki: Tesamoreli kuma yana da tasiri na tsari akan sauran sigogin tsarin jiki a cikin masu cutar HIV. Alal misali, a wasu nazarin, yayin da ma'auni na jiki (BMI) bai nuna wani canje-canje mai mahimmanci ba, ƙwayar jiki ya inganta. Tesamoreli na iya inganta rarraba kitsen jiki ba tare da ya shafi nauyin gabaɗaya ba, rage yawan kitse mai yawa, ƙara yawan abubuwan haɗin jiki kamar tsoka, da haɓaka ingancin jikin marasa lafiya.
Aikace-aikacen Tesamoreli a cikin Fat Metabolism a cikin marasa lafiya na HIV
Yawan Jama'a
Marasa lafiya na HIV tare da ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta ta nuna Tesamoreli ga marasa lafiya da ke fama da ciwon huhu, musamman ma wadanda ke da kitsen visceral da ya wuce kima (misali, kamar yadda binciken CT na ciki ko MRI ya ƙayyade yana nuna visceral adipose tissue [VAT] ƙetare jeri na al'ada). Waɗannan marasa lafiya yawanci suna nuna kiba na ciki, ƙãra kewayen kugu, kuma suna iya nunawa tare da wasu bayyanar cututtuka na rayuwa, kamar juriya na insulin da dyslipidemia.
Kammalawa
A matsayin ingantacciyar wakili na warkewa don ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta a cikin marasa lafiya na HIV, Tesamoreli yana daidaita metabolism mai ta hanyar hanyoyin da yawa, yana taka muhimmiyar rawa wajen rage VAT, inganta haɓakar mai mai hanta, daidaita rarraba mai gaba ɗaya, da haɓaka tsarin jiki.
Sources
[1] Rahman F, Chantal M, Mesquita P, et al. 935. Tasirin Tesamoreli a cikin Mutanen da ke dauke da kwayar cutar HIV tare da kuma ba tare da Kitsen Dorsocervical ba: Binciken Hoc na Post Hoc na Mataki na III Biyu Makafi Sarrafa Ƙaddamarwa [J]. Bude Dandalin Cututtuka masu Yaduwa, 2020,7(Kari_1):S500-S501.DOI:10.1093/ofid/ofaa439.1121.
[2] Rahoton Bincike na asibiti: Tesamoreli (Egrifta) [M]. Ottawa (ON): Hukumar Kanada don Magunguna da Fasaha a Lafiya, 2016.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=30920787&query_hl=1.
Samfura akwai don amfani da bincike kawai:
