Growth hormone-releasing hormone receptor antagonist MIA-602 attenuates cardiopulmonary injury induced by BSL-2 rVSV-SARS-CoV-2 in hACE2 mice.

COVID-19 pneumonia causes acute lung injury and acute respiratory distress syndrome (ALI/ARDS) characterized by early pulmonary endothelial and epithelial injuries with altered pulmonary diffusing capacity and obstructive or restrictive physiology. Growth hormone-releasing hormone receptor (GHRH-R) is expressed in the lung and heart. GHRH-R antagonist, MIA-602, has been reported to modulate immune responses to bleomycin lung injury and inflammation in granulomatous sarcoidosis.

Alveolar epithelial cell growth hormone releasing hormone receptor in alveolar epithelial inflammation.

Growth hormone-releasing hormone (GHRH) is a 44-amino acid peptide that regulates growth hormone (GH) secretion. We hypothesized that GHRH receptor (GHRH-R) in alveolar type 2 (AT2) cells could modulate pro-inflammatory and possibly subsequent pro-fibrotic effects of lipopolysaccharide (LPS) or cytokines, such that AT2 cells could participate in lung inflammation and fibrosis. We used human alveolar type 2 (iAT2) epithelial cells derived from induced pluripotent stem cells (iPSC) to investigate how GHRH-R modulates gene and protein expression.

Synthesis of potent antagonists of receptors for growth hormone-releasing hormone with antitumor and anti-inflammatory activity.

The syntheses and biological evaluation of GHRH antagonists of AVR series with high anticancer and anti-inflammatory activities are described. Compared to our previously reported GHRH antagonist 602 of MIAMI series, AVR analogs contain additional modifications at positions 0, 6, 8, 10, 11, 12, 20, 21, 29 and 30, which induce greater antitumor activities. Five of nineteen tested AVR analogs presented binding affinities to the membrane GHRH receptors on human pituitary, 2-4-fold better than MIA-602.

Growth Hormone-Releasing Hormone in Lung Physiology and Pulmonary Disease.

Growth hormone-releasing hormone (GHRH) is secreted primarily from the hypothalamus, but other tissues, including the lungs, produce it locally. GHRH stimulates the release and secretion of growth hormone (GH) by the pituitary and regulates the production of GH and hepatic insulin-like growth factor-1 (IGF-1). Pituitary-type GHRH-receptors (GHRH-R) are expressed in human lungs, indicating that GHRH or GH could participate in lung development, growth, and repair.

Synthesis and structure-activity studies on novel analogs of human growth hormone releasing hormone (GHRH) with enhanced inhibitory activities on tumor growth.

The syntheses and biological evaluations of new GHRH analogs of Miami (MIA) series with greatly increased anticancer activity are described. In the design and synthesis of these analogs, the following previous substitutions were conserved: D-Arg, Har, Abu, and Nle. Most new analogs had Ala at position 8.

Agonistic analogs of growth hormone releasing hormone (GHRH) promote wound healing by stimulating the proliferation and survival of human dermal fibroblasts through ERK and AKT pathways.

Decreased or impaired proliferation capability of dermal fibroblasts interferes with successful wound healing. Several growth factors tested failed to fully restore the growth of fibroblasts, possibly due to their rapid degradation by proteases. It is therefore critical to find new agents which have stimulatory effects on fibroblasts while being highly resistant to degradation.

Complementary and alternative medicine in reducing radiation-induced skin toxicity.

Radiation therapy-induced acute and late effects, particularly skin toxicities, have significant impact on cancer patients' quality of life and long-term survival. To date, no effective topical agents have been routinely used in the clinical setting to prevent skin toxicity. Using SKH-hr1 hairless mice, we investigated two complementary and alternative medicine in their effects on inflammation and ionizing radiation (IR)-induced skin toxicity: Calendula officinalis (CO) and Ching Wan Hung (CWH).

Synthesis of new potent agonistic analogs of growth hormone-releasing hormone (GHRH) and evaluation of their endocrine and cardiac activities.

In view of the recent findings of stimulatory effects of GHRH analogs, JI-34, JI-36 and JI-38, on cardiomyocytes, pancreatic islets and wound healing, three series of new analogs of GHRH(1-29) have been synthesized and evaluated biologically in an endeavor to produce more potent compounds. "Agmatine analogs", MR-356 (N-Me-Tyr(1)-JI-38), MR-361(N-Me-Tyr(1), D-Ala(2)-JI-38) and MR-367(N-Me-Tyr(1), D-Ala(2), Asn(8)-JI-38), in which Dat in JI-38 is replaced by N-Me-Tyr(1), showed improved relative potencies on GH release upon subcutaneous administration in vivo and binding in vitro. Modification with N-Me-Tyr(1) and Arg(29)-NHCH3 as in MR-403 (N-Me-Tyr(1), D-Ala(2), Arg(29)-NHCH3-JI-38), MR-406 (N-Me-Tyr(1), Arg(29)-NHCH3-JI-38) and MR-409 (N-Me-Tyr(1), D-Ala(2), Asn(8), Arg(29)-NHCH3-JI-38), and MR-410 (N-Me-Tyr(1), D-Ala(2), Thr(8), Arg(29)-NHCH3-JI-38) resulted in dramatically increased endocrine activities.

A rice-derived recombinant human lactoferrin stimulates fibroblast proliferation, migration, and sustains cell survival.

Human lactoferrin (hLF), a glycoprotein of the transferrin family, has recently been shown to stimulate wound repair through its antimicrobial effect and inflammation modulation. A recent study with several non-skin cell lines indicated that hLF may also have a stimulatory effect on cell proliferation. To explore the role of hLF in wound healing, we used recombinant human lactoferrin (holo-rhLF), derived from transgenic rice, to examine the effects of holo-rhLF on cell proliferation, migration, attachment, and survival in a human primary skin fibroblast culture system.

[High output of a Trametes laccase in Pichia pastoris and characterization of recombinant enzymes].

A laccase gene (lacD) from the basidiomycete Trametes sp. 420 was heterologously expressed in Pichia pastoris in two ways, resulting in two recombinant enzymes of rLacDx with native N-terminus and rLacDe with eight additional amino acid residues at N-terminus. The yields of rLacDx and rLacDe in shaken-flask cultures after an 18-day growth were 1.

Inhibition of high-mobility-group A2 protein binding to DNA by netropsin: a biosensor-surface plasmon resonance assay.

The design of small synthetic molecules that can be used to affect gene expression is an area of active interest for development of agents in therapeutic and biotechnology applications. Many compounds that target the minor groove in AT sequences in DNA are well characterized and are promising reagents for use as modulators of protein-DNA complexes. The mammalian high-mobility-group transcriptional factor HMGA2 also targets the DNA minor groove and plays critical roles in disease processes from cancer to obesity.

Specific recognition of AT-rich DNA sequences by the mammalian high mobility group protein AT-hook 2: a SELEX study.

The mammalian high mobility group protein AT-hook 2 (HMGA2) is a transcriptional factor involved in cell differentiation and transformation. Disruption of its normal expression pattern is directly linked to oncogenesis and obesity. HMGA2 contains three "AT-hook" DNA binding domains, which specifically bind to the minor groove of AT-rich sequences.

Large scale preparation of the mammalian high mobility group protein A2 for biophysical studies.

Due to asymmetrical charge distribution of the mammalian high mobility group protein A2 (HMGA2), which makes HMGA2 bind to both cation- and anion-exchange columns, we developed a rapid procedure for purifying HMGA2 in the milligram range. This purification procedure greatly facilitated biophysical studies, which require large amounts of the protein.

High production of laccase by a new basidiomycete, Trametes sp.

A new basidiomycete, Trametes sp. 420, produced laccase at 6,810 U l(-1) (268 mg, 25.4 U mg(-1) protein for guaiacol) in glucose medium and 7,870 U l(-1) (310 mg) in cellobiose medium with induction by 0.

Energetics of binding the mammalian high mobility group protein HMGA2 to poly(dA-dT)2 and poly(dA)-poly(dT).

The mammalian high mobility group protein A2 (HMGA2) is a chromosomal architectural transcription factor involved in oncogenesis and cell transformation. It has three "AT-hook" DNA binding domains, which specifically bind to the minor groove of AT DNAs. The interaction of HMGA2 with poly(dA-dT)2 and poly(dA)poly(dT) has been investigated using the ethidium displacement assay, isothermal titration calorimetry, and UV melting studies.