Ethnobotanical surveys reveal the crucial role of medicinal plants in the primary healthcare system of the Shan people in Myanmar.

ETHNOPHARMACOLOGICAL RELEVANCE: The Shan people of Myanmar live under conditions of longtime social instability and public medical resources inadequate, which tend to strengthen the reliance on local traditional primary healthcare system. The documentation of this kind of resource, however, was rarely and inadequate to support any kind of dynamic trend evaluation. Being an ethnobotanical study, we conducted field survey in the Southern Shan State of Myanmar and aimed to 1) document the local plant species that adopted for primary healthcare purpose, 2) clarify how these species collectively address the broad range of primary medication needs for local people, and 3) lay foundation for dynamic trend evaluation of the role of local medicinal plants under this kind of social and cultural context. MATERIAL AND METHODS: Field surveys were conducted with 124 informants in eight villages. We collected 1259 use reports and documented all the plant species used for treating all the mentioned ailment types. The ailments were translated into their emic meaning and then classified into common disease categories. The top ranked and newly recorded plants or ailment types were analyzed based on historical records from the region. RESULTS: Totally 156 plant species were used for treating 91 ailments belonging to 16 disease categories, with skin problems and digestive tract were the top cited diseases, and with Fabaceae and Lamiaceae were the top cited plant families. A total of 19 newly recorded plant species were suggested as new member of Myanmar medicinal plant list. Besides, we filled the gaps (for 24 species) and enriched the types (for 83 species) of applicable ailments for known Myanmar medicinal plants. CONCLUSION: Our study revealed that the Shan people in Southern Shan State used rich plant species for various therapeutic purposes. Our findings indicate the crucial role of local plant resources for local people's primary healthcare needs and support further study about cultural or regional comparation or historical dynamic trend of the medicinal plants uses in areas facing longtime official or public medical resource inadequate.

Diversity of medicinal plants and their therapeutic usages of Kachin people (Jinghpaw) in the central part of Kachin State, Myanmar.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional medical system plays a major role in healthcare in Kachin State, Myanmar, where long-term political instability persists and conventional healthcare facilities are inadequate. A knowledge of the traditional medicinal plants therefore benefits the Kachin people, yet documentation and records of the uses of these plants are rare. In this study, we attempt to answer the questions on what medicinal plants and how they are used by the Kachin people. AIM OF THE STUDY: We aimed to document knowledge of the traditional medicinal plants and to identify those most frequently used by the Kachin people. MATERIALS AND METHODS: Eighty-two informants from eight villages in three townships were interviewed, and their knowledge of medicinal plants was recorded. The reported ailments were classified to the standard categories of the International Classification of Primary Care-2 (ICPC-2) system. Use reports (UR) were employed to evaluate the knowledge consensus of the informants. RESULTS: We recorded a total of 117 species used as medicinal plants, of which 22 are newly recorded medicinal plant species for Myanmar. The plants belonged to 103 genera in 52 families, and were used to treat a total of 72 ailments from 17 ICPC-2 disease categories. Fabaceae and Lamiaceae were the most highly represented families of medicinal plants, with eleven and eight species used, respectively. The most cited species based on URs were Tinospora cordifolia (Willd.) Hook.f. & Thomson (URs = 39), Oroxylum indicum (L.) Kurz (URs = 28), Aquilaria malaccensis Lam. (URs = 26), Chromolaena odorata (L.) R.M.King & H.Rob. (URs = 24), and Chloranthus elatior Link. (URs = 22). Digestive system disorder was the most prevalent disease category, and was treated with 47 different medicinal plants (URs = 142). Leaves were the most commonly used plant part; decoction was the dominant method of preparation; and oral consumption was the most frequent method of administration. CONCLUSION: Our study documented a list of 117 medicinal plants and their uses in traditional medicine based on the local knowledge of the Kachin people. The study also identified the five most frequently cited species and found that the plants investigated are used to treat a total of 72 diseases. The 642 therapeutic reports we collected showcase a rich and diverse living knowledge of medicinal plant use by the Kachin people. Moreover, we present 22 new medicinal records, enriching the list of known medicinal plants in Myanmar. This exploratory study has enabled us to assemble the local knowledge of the Kachin people into solid dataset that will allow further scientific validation and will potentially contribute to better integration of medicinal plants into the healthcare provision for Kachin people in Myanmar.

Fc-independent functions of anti-CTLA-4 antibodies contribute to anti-tumor efficacy.

Ipilimumab, a monoclonal antibody that recognizes cytotoxic T-lymphocyte associated protein 4 (CTLA-4), was the first immune checkpoint inhibitor approved by the FDA to treat metastatic melanoma patients. Multiple preclinical studies have proposed that Fc effector functions of anti-CTLA-4 therapy are required for anti-tumor efficacy, in part, through the depletion of intratumoral regulatory T cells (Tregs). However, the contribution of the Fc-independent functions of anti-CTLA-4 antibodies to the observed efficacy is not fully understood. H11, a non-Fc-containing single-domain antibody (VHH) against CTLA-4, has previously been demonstrated to block CTLA-4-ligand interaction. However, in vivo studies demonstrated lack of anti-tumor efficacy with H11 treatment. Here, we show that a half-life extended H11 (H11-HLE), despite the lack of Fc effector functions, induced potent anti-tumor efficacy in mouse syngeneic tumor models. In addition, a non-Fc receptor binding version of ipilimumab (Ipi-LALAPG) also demonstrated anti-tumor activity in the absence of Treg depletion. Thus, we demonstrate that Fc-independent functions of anti-CTLA-4 antibodies contributed to anti-tumor efficacy, which may indicate that non-Treg depleting activity of anti-CTLA-4 therapy could benefit cancer patients in the clinic.

Evaluation on Antidiabetic Properties of Medicinal Plants from Myanmar.

OBJECTIVES: To explore the effective and safe medicines for treating diabetes. METHODS: Hydroalcoholic extracts of 130 medicinal plants belonging to 66 families were evaluated using porcine pancreatic lipase (PPL) inhibition and glucose uptake methods together with a literature review. RESULTS: The extracts of 22 species showed the PPL inhibition activity; 18 extracts of 15 species stimulated glucose uptake in 3T3-L1 adipocytes. Among them, Mansonia gagei J.R. Drumm., Mesua ferrea L., and Centella asiatica (L.) Urb. exhibited both activities. The extracts of Caladium lindenii (André) Madison rhizomes and Azadirachta indica A. Juss. leaves presented the utmost lipase inhibitory activity with IC50 of 6.86 ± 0.25 and 11.46 ± 0.06 µg/mL, respectively. The extracts of Coptis teeta Wall. rhizomes and Croton tiglium L. seeds stimulated the maximum glucose uptake. Ten species are reported to have antidiabetic activity for the first time. Flavonoids and triterpenoids are the dominant antidiabetic compounds in selected medicinal plants from Myanmar. CONCLUSIONS: P. zeylanica, L. cubeba, H. crenulate, M. gagei, C. teeta, and M. ferrea are worthy to advance further study according to their strong antidiabetic activities and limited research on effects in in vivo animal studies, unclear chemical constitutes, and safety.

The secret of health in daily cuisine: typical healthy vegetables in local markets in central Myanmar.

BACKGROUND: Central Myanmar is located in the Indo-Burma biodiversity hotspot, and the Bamar people are the main ethnic group, which settled there over 1000 years ago. Despite being the core region of the country, central Myanmar has been ignored in previous ethnobotanical studies. Local healthy foods and knowledge are regarded as treasures for resource development and pharmaceutical drug discovery, and market surveys are a good strategy in ethnobotanical research. Thus, we collected and documented typical vegetables and local knowledge in local markets and then analysed the diversity and local knowledge of these vegetables. MATERIALS AND METHODS: Observations and interviews were used in the field study, and 10 markets and fairs were selected in central Myanmar. A total of 277 vegetable stalls or shops were visited. We compared the local knowledge we collected with selected important and typical herbal books on traditional Myanmar medicine. Quantitative analysis, including frequency of citation (FC), relative frequency of citation (RFC) and use value (UV), was used to assess the diversity and local knowledge of these vegetables. RESULTS: A total of 132 plant taxa from 47 botanical families and 116 genera were collected. Most (106 taxa, 80.3%) of these vegetables were cited by the informants as functional foods that had health benefits, while others were regarded as merely "good for health". The main health function of the vegetables was treating digestive problems. Sixty-four species were recorded in selected herbal books on traditional Myanmar medicine, and forty-seven taxa were not recorded in these books but were nonetheless used as healthy vegetables by local people. Twenty-eight species of vegetables were collected from wild places. CONCLUSION: The diversity and local knowledge of healthy vegetables in central Myanmar were rich. Nevertheless, the diversity of wild vegetables was seemingly relatively low. The possible reason was that we counted only the vegetables that were from entirely wild sources as "wild vegetables". The most frequently cited vegetables were commonly cultivated species, which reflects the fact that plants cultivated on a large scale comprise the major source of vegetables. Some lesser known vegetables could reflect the unique food culture of local people, but most of these were cited only a few times by the interviewees, which caused low UV and RFC rankings for them in the league table. In addition, future research should pay more attention to the food safety of these vegetables.

The uses of fig (Ficus) by five ethnic minority communities in Southern Shan State, Myanmar.

BACKGROUND: Most regions of Myanmar fall within the Indo-Burma Biodiversity Hotspot and are threatened with biodiversity loss. Development of a comprehensive framework for sustainable development is crucial. Figs are ecological keystone species within these regions and are also important for traditional spiritual food and health uses, which often have accompanying conservation practices. The traditional use and management of figs may offer clues to help guide the development of national policies for sustainable development. In this study, we showcase the rich ethnobotanical knowledge as well as the variety of collection and conservation practices of figs among five ethnic groups in Southern Shan State. METHODS: We performed both key informant and semi-structured interviews with 114 informants from five ethnic groups. Their uses for figs were categorized according to local practices and recipes. Informants were asked about trends in conservation status over the past 10 years and any conservation-related customs and practices. Data were analyzed quantitatively with common quantitative ethnobotany indices, the use report (UR) and use value (UV). RESULTS: Informants reported the uses of eight fig species (Ficus auricularta, F. concinna, F. geniculata, F. hispida, F. racemosa, F. religiosa, F. semicordata, and F. virens). F. geniculata and F. virens were most useful (UR = 228) and were used by all five ethnic groups, corresponding to a high use value (UV = 2). Treatments for 16 diseases were reported from seven species. Household consumption, economic and sacred uses were accompanied by sustainable practices of harvest and protection. Traditional taboos, in situ and ex situ conservation were common especially for highly demanded species (F. geniculata and F. virens) and the sacred fig F. religiosa. CONCLUSION: Findings suggest that figs are useful for food (all informants) and medicine (13.16% of the informants) in the study area. Traditional taboos, in situ and ex situ conservation practices help to maintain sustainable utilization of locally important figs. This is an early contribution to the traditional knowledge of edible figs. Although similar uses have been reported in neighboring countries for seven of the fig species, the ethnobotanical use of F. concinna is novel.

Chemical Constituents from the Whole Plant of Cuscuta reflexa.

Two new 2H-pyran-2-one glucosides, cuscutarosides A (1) and B (2), and one new steroidal glucoside, 7ß-methoxy-ß-sitosterol 3-O-ß-glucopyranoside (3), together with 12 known compounds (4-15) were isolated from the whole plant of Cuscuta reflexa (Convolvulaceae) collected from Myanmar. The chemical structures of these new compounds were elucidated based on extensive spectroscopic analysis. The antiobesity activity of these isolates was evaluated using porcine pancreatic lipase (PPL), and the antiplatelet aggregation activity was screened using rabbit platelets induced by thrombin, platelet-activating factor (PAF), arachidonate (AA), or collagen. 7ß-Methoxy-ß-sitosterol 3-O-ß-glucopyranoside (3) showed weak PPL inhibitory activity. Cuscutaroside A (1), its acetylated derivative (1a), and scrophenoside B (8) showed weak inhibitory activity against rabbit platelet aggregation induced by collagen. Compound 1a also showed inhibitory activity against rabbit platelet aggregation induced by AA.

Investigation on the Antibacterial and Anti-T3SS Activity of Traditional Myanmar Medicinal Plants.

Myanmar has a rich pool of, but less known, medicinal plants with traditional knowledge. In this study, we aimed to investigate the inhibitory activity of traditional Myanmar medicinal plants against the type III secretion system (T3SS) of Salmonella enterica serovar Typhimurium UK-1 χ8956 and the intestinal disease-caused by microbes including S. enterica serovar Typhimurium UK-1 χ8956, Proteusbacillus vulgaris CPCC 160013, Escherichia coli CICC 10003, and Staphylococcus aureus ATCC 25923. The EtOH extracts of 93 samples were used to screen the inhibitory activities against the secretion of T3SS effector proteins SipA/B/C/D of S. enterica and the antibacterial activity against S. enterica, P. vulgaris, E. coli, and S. aureus. Out of 71 crude drugs traditionally used, 18 were proofed to be effective either on the growth inhibition of tested bacteria and/or as inhibitors for the T3SS. The EtOH extracts of five plants, Luvunga scandens (Roxb.) Buch.-Ham. ex Wight & Arn. (My7), Myrica nagi Thunb. (My11), Terminalia citrina Roxb. ex Fleming (My21), Thymus vulgaris L. (My49), and Cinnamomum bejolghota (Buch.-Ham.) Sweet (My104), showed potent inhibitory activities against the secretion of T3SS proteins SipA/B/C/D of S. enterica serovar Typhimurium UK-1 χ 8956. Mansonia gagei J.R.Drumm (My3) and Mesua ferrea (Roxb.) L. (My10) showed strong antibacterial activities against P. vulgaris and S. aureus. This study provided the first scientific evidence of T3SS prohibiting and antibacterial properties for the traditional knowledge in Myanmar of using plants as medicines for treating infections and gastrointestinal disease. Further researches are proposed to discover the active chemical compounds and mechanism of L. scandens (Roxb.) Buch.-Ham. ex Wight & Arn, M. nagi Thunb., T. citrina Roxb. ex Fleming, T. vulgaris L., and C. bejolghota (Buch.-Ham.) Sweet as antivirulence drugs and the potential of M. gagei J.R.Drumm and M. ferrea L. as new broad spectrum plant antibiotics.

XBP1s activation can globally remodel N-glycan structure distribution patterns.

Classically, the unfolded protein response (UPR) safeguards secretory pathway proteostasis. The most ancient arm of the UPR, the IRE1-activated spliced X-box binding protein 1 (XBP1s)-mediated response, has roles in secretory pathway maturation beyond resolving proteostatic stress. Understanding the consequences of XBP1s activation for cellular processes is critical for elucidating mechanistic connections between XBP1s and development, immunity, and disease. Here, we show that a key functional output of XBP1s activation is a cell type-dependent shift in the distribution of N-glycan structures on endogenous membrane and secreted proteomes. For example, XBP1s activity decreased levels of sialylation and bisecting GlcNAc in the HEK293 membrane proteome and secretome, while substantially increasing the population of oligomannose N-glycans only in the secretome. In HeLa cell membranes, stress-independent XBP1s activation increased the population of high-mannose and tetraantennary N-glycans, and also enhanced core fucosylation. mRNA profiling experiments suggest that XBP1s-mediated remodeling of the N-glycome is, at least in part, a consequence of coordinated transcriptional resculpting of N-glycan maturation pathways by XBP1s. The discovery of XBP1s-induced N-glycan structural remodeling on a glycome-wide scale suggests that XBP1s can act as a master regulator of N-glycan maturation. Moreover, because the sugars on cell-surface proteins or on proteins secreted from an XBP1s-activated cell can be molecularly distinct from those of an unactivated cell, these findings reveal a potential new mechanism for translating intracellular stress signaling into altered interactions with the extracellular environment.

RNA polymerase pausing and nascent-RNA structure formation are linked through clamp-domain movement.

The rates of RNA synthesis and the folding of nascent RNA into biologically active structures are linked via pausing by RNA polymerase (RNAP). Structures that form within the RNA-exit channel can either increase pausing by interacting with RNAP or decrease pausing by preventing backtracking. Conversely, pausing is required for proper folding of some RNAs. Opening of the RNAP clamp domain has been proposed to mediate some effects of nascent-RNA structures. However, the connections among RNA structure formation and RNAP clamp movement and catalytic activity remain uncertain. Here, we assayed exit-channel structure formation in Escherichia coli RNAP with disulfide cross-links that favor closed- or open-clamp conformations and found that clamp position directly influences RNA structure formation and RNAP catalytic activity. We report that exit-channel RNA structures slow pause escape by favoring clamp opening through interactions with the flap that slow translocation.

Antisense oligonucleotide-stimulated transcriptional pausing reveals RNA exit channel specificity of RNA polymerase and mechanistic contributions of NusA and RfaH.

Transcript elongation by bacterial RNA polymerase (RNAP) is thought to be regulated at pause sites by open versus closed positions of the RNAP clamp domain, pause-suppressing regulators like NusG and RfaH that stabilize the closed-clampRNAP conformation, and pause-enhancing regulators like NusA and exit channel nascent RNA structures that stabilize the open clamp RNAP conformation. However, the mutual effects of these protein and RNA regulators on RNAP conformation are incompletely understood. For example, it is unknown whether NusA directly interacts with exit channel duplexes and whether formation of exit channel duplexes and RfaH binding compete by favoring the open and closed RNAP conformations. We report new insights into these mechanisms using antisense oligonucleotide mimics of a pause RNA hairpin from the leader region of the his biosynthetic operon of enteric bacteria like Escherichia coli. By systematically varying the structure and length of the oligonucleotide mimic, we determined that full pause stabilization requires an RNA-RNA duplex of at least 8 bp or a DNA-RNA duplex of at least 11 bp; RNA-RNA duplexes were more effective than DNA-RNA. NusA stimulation of pausing was optimal with 10-bp RNA-RNA duplexes and was aided by single-stranded RNA upstream of the duplex but was significantly reduced with DNA-RNA duplexes. Our results favor direct NusA stabilization of exit channel duplexes, which consequently affect RNAP clamp conformation. Effects of RfaH, which suppresses oligo-stabilization of pausing, were competitive with antisense oligonucleotide concentration, suggesting that RfaH and exit channel duplexes compete via opposing effects on RNAP clamp conformation.

RNA transcript 3'-proximal sequence affects translocation bias of RNA polymerase.

Translocation of RNA polymerase on DNA is thought to involve oscillations between pretranslocated and posttranslocated states that are rectified by nucleotide addition or pyrophosphorolysis. The pretranslocated register is also a precursor to transcriptional pause states that mediate regulation of transcript elongation. However, the determinants of bias between the pretranslocated and posttranslocated states are incompletely understood. To investigate translocation bias in multisubunit RNA polymerases, we measured rates of pyrophosphorolysis, which occurs in the pretranslocated register, in minimal elongation complexes containing T. thermophilus or E. coli RNA polymerase. Our results suggest that the identity of RNA:DNA nucleotides in the active site are strong determinants of susceptibility to pyrophosphorolysis, and thus translocation bias, with the 3' RNA nucleotide favoring the pretranslocated state in the order U > C > A > G. The preference of 3' U vs G for the pretranslocated register appeared to be universal among both bacterial and eukaryotic RNA polymerases and was confirmed by exonuclease III footprinting of defined elongation complexes. However, the relationship of pyrophosphate concentration to the rate of pyrophosphorolysis of 3' U-containing versus 3' G-containing elongation complexes did not match predictions of a simple mechanism in which 3'-RNA seqeunce affects only translocation bias and pyrophosphate (PPi) binds only to the pretranslocated state.

The bridge helix coordinates movements of modules in RNA polymerase.

The RNA polymerase 'bridge helix' is a metastable α-helix that spans the leading edge of the enzyme active-site cleft. A new study published in BMC Biology reveals surprising tolerance to helix-disrupting changes in a region previously thought crucial for translocation, and suggests roles for two hinge-like segments of the bridge helix in coordinating modules that move during the nucleotide-addition cycle.

The Arabidopsis thaliana Myo-inositol 1-phosphate synthase1 gene is required for Myo-inositol synthesis and suppression of cell death.

l-myo-inositol 1-phosphate synthase (MIPS; EC 5.5.1.4) catalyzes the rate-limiting step in the synthesis of myo-inositol, a critical compound in the cell. Plants contain multiple MIPS genes, which encode highly similar enzymes. We characterized the expression patterns of the three MIPS genes in Arabidopsis thaliana and found that MIPS1 is expressed in most cell types and developmental stages, while MIPS2 and MIPS3 are mainly restricted to vascular or related tissues. MIPS1, but not MIPS2 or MIPS3, is required for seed development, for physiological responses to salt and abscisic acid, and to suppress cell death. Specifically, a loss in MIPS1 resulted in smaller plants with curly leaves and spontaneous production of lesions. The mips1 mutants have lower myo-inositol, ascorbic acid, and phosphatidylinositol levels, while basal levels of inositol (1,4,5)P(3) are not altered in mips1 mutants. Furthermore, mips1 mutants exhibited elevated levels of ceramides, sphingolipid precursors associated with cell death, and were complemented by a MIPS1-green fluorescent protein (GFP) fusion construct. MIPS1-, MIPS2-, and MIPS3-GFP each localized to the cytoplasm. Thus, MIPS1 has a significant impact on myo-inositol levels that is critical for maintaining levels of ascorbic acid, phosphatidylinositol, and ceramides that regulate growth, development, and cell death.

Differential feeding responses to central alpha-melanocyte stimulating hormone in genetically low and high body weight selected lines of chickens.

This study was conducted to compare the effects of central alpha-MSH, a potent anorexigenic signal, in lines of chickens that have undergone long-term divergent selection for low (LWS) or high (HWS) body weight. Chicks from both lines were centrally injected with 0, 24, 120 or 600 pmol alpha-MSH and feed and water intake were concurrently measured thereafter for a total of 180 min. The LWS line responded to all doses of alpha-MSH with a similar potent decrease in feed intake at all observation times. The HWS line only responded to 600 pmol alpha-MSH with decreased feed intake. alpha-MSH did not influence water intake in either line. To determine if differential hypothalamic signaling was associated with the anorexigenic effect, c-Fos immunoreactivity was measured in appetite-related hypothalamic nuclei after 600 pmol central alpha-MSH injections. c-Fos immunoreactivity was increased in the dorsomedial hypothalamus, paraventricular nucleus (PVN) and ventromedial hypothalamus in both lines after alpha-MSH; however, the magnitude of increase was greater in LWS than in HWS chicks at the PVN (136% vs. 47% increase over controls, respectively). Based on behavior observations, the number of feeding and exploratory pecks is decreased with greater magnitude after alpha-MSH in the LWS line. Additionally, alpha-MSH was associated with increased deep rest in both lines, and may be a secondary effect to reduced ingestion. These data support that the LWS line has a lower threshold for the anorexigenic effect of central alpha-MSH while in the HWS line this threshold is higher, and that this difference may be associated with differential hypothalamic signaling. Genetic variation exists in the threshold of anorexigenic response for central alpha-MSH in LWS and HWS lines of chickens with possible implications to other species including humans.

Theoretical study of the dynamics of AR collisions with C2H6 and C2F6 at hyperthermal energy.

We present a classical-trajectory study of the dynamics of high-energy (5-12 eV) collisions between Ar atoms and the C2H6 and C2F6 molecules. We have constructed the potential-energy surfaces for these systems considering separately the Ar-molecule interactions (intermolecular potential) and the interactions within the molecule (intramolecular potential). The intermolecular surfaces consist of pairwise empirical potentials derived from high-accuracy ab initio calculations. The intramolecular potentials for C2H6 and C2F6 are described using specific-reaction-parameters semiempirical Hamiltonians and are calculated "on the fly", i.e., while the trajectories are evolving. Trajectory analysis shows that C2F6 absorbs more energy than C2H6 and is more susceptible to collision-induced dissociation (CID). C-C bond-breakage processes are more important than C-H or C-F bond breakage at the energies explored in this work. Analysis of the reaction mechanism for CID processes indicates that, although C-C breakage is mostly produced by side-on collisions, head-on collisions are more efficient in producing C-F or C-H dissociation. Our results suggest that high-energy collisions between closed-shell species of the natural low-Earth-orbit environment and spacecraft can contribute to the observed degradation of polymers that coat spacecraft surfaces.