söndag 31 mars 2019

2 nya forskningsrapporter

I fredags (PHI dagen) fick 12 kinesiska forskare sina studier beträffande kroppens immunförsvar via makrofager förstärkta med ämnet Momordicoside G publicerade i den vetenskapliga skriften Frontiers in Pharmacology.


Deras gärning beskrivs enligt följande :
This section on Pharmacology of Anti-Cancer Drugs is devoted to the publication of high quality research concerning all aspects of cancer and benign neoplasm drug treatment. The scope of the specialty section encompasses studies related to drugs targeting tumor cells, but also the various components of the tumor microenvironment, including non-tumor cells (e.g., endothelial cells, macrophages, lymphocytes, and fibroblasts), and stress conditions such as hypoxia and acidity. Relevant to the specialty section is experimental, pre-clinical or clinical research addressing the potential and limitations of new antineoplastic and antimetastatic therapies issued from inventive drug design or bioguided isolation from plants. Cancer treatment is an area of medicine where the concepts of multi-modality, drug delivery, and personalized medicine are the most advanced. Therefore, Pharmacology of Anti-Cancer Drugs will also have a particular interest in the following issues: The synergy between chemotherapy and other anticancer modalities, including radio-, immuno- and gene therapy; the use of nanoscale particles or targeting moieties to improve drug bioavailability; and the identification of biomarkers derived from proteomics, and genomics or imaging technologies to predict response or resistance to drug treatment.

Man beskriver sin impact såhär :
Men tillbaka till studien.
De kinesiska forskarna har studerat hur makrofager kan fås att bli effektivare vid en svår lungcancer. Man berättar att, trots senare års försök med andra behandlingsformer, har inte den 5-åriga överlevnadsfrekvensen förbättrats nämnvärt. Forskarna har då studerat ämnet Momordicoside G, utvunnet ur medicinalväxten Momordica charantia, som sen tidigare är känd för att stimulera sårläkning vid vävnadsskador. Här testade man att bryta ner växtens befrämjande beståndsdelar i minsta partiklar och applicerade dessa in i makrofager ner på minsta proteinnivå.
Vi snackar tålamod och tidskrävande forskning.Förmodligen därför det krävdes 12 forskarkompetenser för att nå resultat. Men hursom, forskarna fick träff på en specifik kombination av bägge beskrivna, som visade på förbättrad effektivitet för kroppens immunförsvar vid just svårartad lungcancer.

Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma Lesions

                                            Front. Pharmacol., 29 March 2019
Abstract
Momordicoside G is a bioactive component from Momordica charantia, this study explores the contributions of macrophages to the effects of momordicoside G on lung injury and carcinoma lesion. In vitro, when administered at the dose that has no effect on cell viability in M2-like macrophages, momordicoside G decreased ROS and promoted autophagy and thus induced apoptosis in M1-like macrophages with the morphological changes. In the urethane-induced lung carcinogenic model, prior to lung carcinoma lesions, urethane induced obvious lung injury accompanied by the increased macrophage infiltration. The lung carcinoma lesions were positively correlated with lung tissue injury and macrophage infiltration in alveolar cavities in the control group, these macrophages showed mainly a M1-like (iNOS+/CD68+) phenotype. ELISA showed that the levels of IL-6 and IL-12 were increased and the levels of IL-10 and TGF-β1 were reduced in the control group. After momordicoside G treatment, lung tissue injury and carcinoma lesions were ameliorated with the decreased M1-like macrophages and the increased M2-like (arginase+/CD68+) macrophages, whereas macrophage depletion by liposome-encapsulated clodronate (LEC) decreased significantly lung tissue injury and carcinoma lesions and also attenuated the protective efficacy of momordicoside G. The M2 macrophage dependent efficacy of momordicoside G was confirmed in a LPS-induced lung injury model in which epithelial closure was promoted by the transfer of M2-like macrophages and delayed by the transfer of M1-like macrophages. To acquire further insight into the underlying molecular mechanisms by which momordicoside G regulates M1 macrophages, we conduct a comprehensive bioinformatics analysis of momordicoside G relevant targets and pathways involved in M1 macrophage phenotype. This study suggests a function of momordicoside G, whereby it selectively suppresses M1 macrophages to stimulate M2-associated lung injury repair and prevent inflammation-associated lung carcinoma lesions.

Jag klipper som vanligt in enbart PHI-relaterat.

Cell Culture and Assay

Cells were analyzed by Laser holographic cell imaging and analysis system (HoloMonitor M4, Phiab, Sweden). 

Figure 2. Momordicoside G induces M1 macrophage apoptosis in vitro (A) Cell apoptosis detected with Annexin V-FITC Apoptosis kit (n = 5). (B,C) Morphological changes analyzed with Laser holographic cell imaging and analysis system (n = 5, 20×). (D) NO (n = 5) (E) IL-12 (n = 5) (F) IL-10 (n = 5) (G) TGF-β1 (n = 5) The data presents mean ± SD, the experiments were repeated 3 times, and statistical significance was determined by a t-test. P < 0.05, ∗∗P < 0.01 vs. control.

Från studiens slutsatser
- In summary, M2-like macrophages play an important role in wound healing and tissue homeostasis, our findings suggest several potential clinical implications.
First, there will not be carcinogenesis if tissue injury can be timely and completely cured.
Second, Momordicoside G can selectively suppress M1 to maintain M2 macrophages for lung injury repair and therefore prevent inflammation-related lung carcinogenesis.
Third, the combination of momordicoside G and M2 macrophages synergistically promote lung injury repair and can be a novel strategy for cancer chemoprevention.

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 Sen till forskningsrapport nummer 2.

Även här är det kinesiska forskare i farten.
Närmare bestämt 8 st som fått sina studier publicerade i organet Bioorganic & Medicinal Chemistry

Man beskriver sin gärning enligt följande :
Bioorganic & Medicinal Chemistry publishes complete accounts of research of outstanding significance and timeliness on all aspects of molecular interactions at the interface of chemistry and biology, together with critical review articles. The journal publishes reports of experimental results in medicinal chemistry, chemical biology and drug discovery and design, emphasizing new and emerging advances and concepts in these fields. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents.

Denna forskningsrapport berör det jag editerade in i förra inlägget. Nämligen behandlingsformen PDT, PhotoDynamicTherapy / Fotodynamisk terapi som wiki kan berätta mer om.
- Fotodynamisk terapi (vanligen förkortat PDT efter eng. "Photodynamic Therapy") utvecklades till en praktiskt användbar klinisk behandlingsmetod under 1980-talet.
Metoden är en tertiär behandlingsmetod för främst cancer som innefattar tre nödvändiga komponenter: en fotosensibiliserare, ljus samt syre.
Amerikanska National Cancer Institute  berättar mer om Photodynamic Therapy for Cancer.


Men till själva studien betitlad :

Synthesis, Characterization, and Photodynamic Therapy Activity of 5,10,15,20-Tetrakis(carboxyl)porphyrin

                                            Available online 27 March 2019
Som forskningsrapporten härovanför berör även denna studie lungcancer.

Abstract
Water-soluble porphyrins are considered promising drug candidates for photodynamic therapy (PDT). This study investigated the PDT activity of a new water-soluble, anionic porphyrin (1-Zn), which possesses four negative charges. The photodynamic anticancer activity of 1-Zn was investigated by the MTT assay, with mTHPC as a positive control. The cellular distribution was determined by fluorescence microscopy. Holographic and phase contrast images were recorded after 1-Zn treatment with a HoloMonitor™ M3 instrument. The inhibition of A549 cell growth achieved by inducing apoptosis was investigated by flow cytometry and fluorescence microscopy. DNA damage was investigated by the comet assay. The expression of apoptosis-related proteins was also measured by western blot assays. 1-Zn had better phototoxicity against A549 cells than HeLa and HepG2 cancer cells. Interestingly, 1-Zn was clearly located almost entirely in the cell cytoplasmic region/organelles. The late apoptotic population was less than 1.0% at baseline in the untreated and only light-treated cells and increased to 40.5% after 1-Zn treatment and irradiation (P<0.05). 1-Zn triggered significant ROS generation after irradiation, causing ΔΨm disruption (P<0.01) and DNA damage. 1-Zn induced A549 cell apoptosis via the mitochondrial apoptosis pathway. In addition, 1-Zn bound in the groove of DNA via an outside binding mode by pi-pi stacking and hydrogen bonding. 1-Zn exhibits good photonuclease activity and might serve as a potential photosensitizer (PS) for lung cancer cells.



Hur ett nytt vattenlösligt porfyrin, 1-Zn, kan förstärka behandlingsformen PDT. Även i detta fallet alltså kopplat till lungcancer.
Wiki är en outsinlig källa till information och berättar mer om Porfyriner :
- Porfyriner är en grupp kemiska föreningar, som ingår i ett flertal biologiska system, bland annat är de produkter i bildningen av hem och klorofyll. Porfyriner består huvudsakligen av kol- och väteatomer, men i de heterocykliska och aromatiska ringstrukturer som kolatomerna bildar ingår även kväveatomer. Grundstrukturen som är gemensam för alla porfyriner är en tetrapyrrolring som är sammanbunden med metenbryggor. Naturligt förekommande porfyriner kategoriseras genom antalet karboxylgrupper som är substituerade på ringstrukturen och varierar mellan två och åtta stycken. Uroporfyrin (åtta st syragrupper), coproporfyrin (4 st syragrupper) samt protoporfyrin IX (2 st syragrupper) är exempel på porfyriner som bildas vid hemsyntesen. Porfyriner är på grund av sin aromatiska ringstruktur, naturligt förekommande pigment och har fluorescerande egenskaper med absorptionsband mellan 390 och 425 nm.

Studien är som synes låst och vi får enbart tillgång till abstractet. Men de är snälla och berättar i den att de använt sig av 2 mikroskopitekniker. Fluoroscerande (som inte bevärdigas närmare !) och teknik nr 2 som de däremot gärna namnger.
- Holographic and phase contrast images were recorded after 1-Zn treatment with a HoloMonitor™ M3 instrument.
Det tackar vi för.

Edit. Nu även uppmärksammad i Kina.

Min kommentar
Det börjar komma in en strid ström av forskningsrapporter baserade på PHI´s teknik.
Har ni noterat det?
Med dessa 2 får jag det till 10 st enbart från årsskiftet.
Utan att veta bestämt tror jag att vi kan beskåda den s.k. ketchupeffekten även inom detta område.
Användare börjar få kläm på tekniken och har lärt sig att använda sina resp HoloMonitor´s även vid studier som man tidigare inte tänkt tekniken var applicerbar inom.
Bådar gott.

                                           Mvh the99

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