Nervogenic Acid Derivatives and Phenanthrenes from Liparis nervosa and Their Antimicrobial and Immunosuppressive Activities.

Two new nervogenic acid derivatives liparisnervosides Q (1) and R (5), as well as five known nervogenic acid derivatives (2-4, 6, 7) and four phenanthrenes (8-11) were isolated from the whole plant of Liparis nervosa (Thunb. ex A. Murray) Lindl.. Their structures were detremined using extensive spectroscopic techniques, including 1D, 2D NMR, and HR-ESI-MS, and acid hydrolysis. Furthermore, their antimicrobial and immunosuppressive activities were evaluated. Nervosine VII (3) exhibited antimicrobial activity against Staphylococcus aureus with an MIC of 62.5 µg/mL and inhibited the proliferation of human T cells with an IC50 value of 9.67±0.96 µM. These findings contribute to our understanding of the potential pharmacological properties of these compounds.

Comparison of maxillary anterior mathematical proportions among 3 dental arch forms.

STATEMENT OF PROBLEM: Race and sex differences in the mathematical proportions of maxillary anterior teeth have been evaluated. However, studies exploring the relationship between the mathematical proportion of maxillary anterior teeth and maxillary dental arch form are lacking. PURPOSE: The purpose of this clinical study was to determine if a correlation exists between the mathematical proportions of maxillary anterior teeth and 3 dental arch forms. MATERIAL AND METHODS: Three hundred young participants were recruited according to predefined criteria, and images and maxillary casts were obtained. The perceived width and length of the maxillary anterior teeth were measured on the images by using a software program, and mathematical proportions, including width ratios and width-to-length ratios, were calculated for each. The casts were used to categorize each specimen into tapered, ovoid, or square groups by using a specific classification method, and the width ratios and width-to-height ratios of the 3 dental arch forms were compared. Statistical analysis was performed by using analysis of variance (ANOVA) or the Kruskal-Wallis H test to compare the mathematical proportions of maxillary anterior teeth among the 3 dental arch forms (α=.05). The intraclass correlation coefficient (ICC) was used to test the reliability of the investigators. RESULTS: Except for the width-to-length ratios of the central incisor, mathematical proportions were affected by the dental arch form. The perceived width ratios of the maxillary lateral incisor-to-central incisor gradually increased from the tapered arch to the ovoid arch and from the ovoid arch to the square arch, with mean ±standard deviation values of 0.71 ±0.04, 0.73 ±0.05, and 0.79 ±0.06, respectively. For the maxillary perceived width ratios of canine-to-lateral incisor, the ovoid arch had the maximum perceived width ratios (0.86 ±0.10), followed by the tapered (0.82 ±0.10) and square arches (0.77 ±0.11). The width-to-length ratios of the central incisor were not affected by the arch form (P=.075), and the width-to-length ratios of the lateral incisor increased as the arch form became flat, with respective values of 0.70 ±0.10, 0.74 ±0.10, and 0.76 ±0.10. For the width-to-length ratios of the canine, the ovoid arch had the maximum perceived width ratios (0.58 ±0.10), followed by the tapered (0.53 ±0.10) and square arches (0.52 ±0.10). CONCLUSIONS: The mathematical proportions varied among the 3 dental arch forms, and the dental arch form should be considered during the prosthodontic design of maxillary anterior teeth.

Indigoidine biosynthesis triggered by the heavy metal-responsive transcription regulator: a visual whole-cell biosensor.

During the last few decades, whole-cell biosensors have attracted increasing attention for their enormous potential in monitoring bioavailable heavy metal contaminations in the ecosystem. Visual and measurable output signals by employing natural pigments have been demonstrated to offer another potential choice to indicate the existence of bioavailable heavy metals in recent years. The biosynthesis of the blue pigment indigoidine has been achieved in E. coli following heterologous expression of both BpsA (a single-module non-ribosomal peptide synthetase) and PcpS (a PPTase to activate apo-BpsA). Moreover, we demonstrated herein the development of the indigoidine-based whole-cell biosensors to detect bioavailable Hg(II) and Pb(II) in water samples by employing metal-responsive transcriptional regulator MerR and PbrR as the sensory elements, and the indigoidine biosynthesis gene cluster as a reporter element. The resulting indigoidine-based biosensors presented a good selectivity and high sensitivity to target metal ions. High concentration of target metal exposure could be clearly recognized by the naked eye due to the color change by the secretion of indigoidine, and quantified by measuring the absorbance of the culture supernatants at 600 nm. Dose-response relationships existed between the exposure concentrations of target heavy metals and the production of indigoidine. Although fairly good linear relationships were obtained in a relatively limited concentration range of the concentrations of heavy metal ions, these findings suggest that genetically controlled indigoidine biosynthesis triggered by the MerR family transcriptional regulator can enable a sensitive, visual, and qualitative whole-cell biosensor for bioindicating the presence of bioaccessible heavy metal in environmental water samples. KEY POINTS: • Biosynthesis pathway of indigoidine reconstructed in a high copy number plasmid in E. coli. • Visual and colorimetric detection of Hg(II) and Pb(II) by manipulation of indigoidine biosynthesis through MerR family metalloregulator. •Enhanced detection sensitivity toward Hg(II) and Pb(II) achieved using novel pigment-based whole-cell biosensors.

A benzoxazole derivative PO-296 inhibits T lymphocyte proliferation by the JAK3/STAT5 signal pathway.

Immunosuppressants have shown striking achievements in treating autoimmune diseases in recent years. It is urgent to develop more immunosuppressants to provide more options for patients. PO-296 [2-(6-chlorobenzo[d]oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol] was identified as a novel benzoxazole derivative. We observed that it exhibits an obvious immunosuppressive activity to T lymphocytes. PO-296 significantly inhibited the proliferation of activated human T lymphocyte without cytotoxicity. Moreover, PO-296 did not affect the expression of cluster of differentiation (CD)-25 or CD69 but induced T lymphocyte cycle arrest in the G0/G1 phase. Furthermore, PO-296 inhibited interleukin (IL)-6, IL-17, and interferon gamma expression but had no effect on IL-2, IL-4, or IL-10. Yet, importantly, PO-296 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5), increased the phosphorylation of p70S6K, but did not affect the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mitogen-activated protein kinase pathway. In conclusion, these findings indicate that PO-296 inhibits human activated T-lymphocyte proliferation by affecting the janus kinase 3 (JAK3)/STAT5 pathway. PO-296 possesses a potential lead compound for the design and development of new immunosuppressants for the treatment of autoimmune diseases.

Bioactivity-Guided Isolation and Identification of New and Immunosuppressive Monoterpenoid Indole Alkaloids from Rauvolfia yunnanensis Tsiang.

Three new 11-hydroxyburnamine (1) and rauvoyunnanines A-B (2-3), and fourteen known (4-17) monoterpenoid indole alkaloids were isolated from the total alkaloids extract of Rauvolfia yunnanensis, which exhibited promising immunosuppressive activity on T cell proliferation in preliminary screening. Their structures were determined by analysis of high-resolution electrospray ionization mass (HRESIMS), ultraviolet (UV) and nuclear magnetic resonance (NMR) data, and by comparison with the literature. All the alkaloids were evaluated for inhibitory activity on T cell proliferation. Among them, one new compound (1) and reserpine (6) exhibited moderate immunosuppressive activity, with IC50 values of 5.9 µM and 5.0 µM, respectively.

Grape hexokinases are involved in the expression regulation of sucrose synthase- and cell wall invertase-encoding genes by glucose and ABA.

Hexokinase (HXK, EC 2.7.1.1) is a multifunctional protein that both is involved in catalyzing the first step of glycolysis and plays an important role in sugar signaling. However, the supporting genetic evidence on hexokinases (CsHXKs) from grape (Vitis vinifera L. cv. Cabernet Sauvignon) berries has been lacking. Here, to investigate the role of CsHXK isoforms as glucose (Glc) and abscisic acid (ABA) sensors, we cloned two hexokinase isozymes, CsHXK1 and CsHXK2 with highly conserved genomic structure of nine exons and eight introns. We also found adenosine phosphate binding, substrate recognition and connection sites in their putative proteins. During grape berry development, the expression profiles of two CsHXK isoforms, sucrose synthases (SuSys) and cell wall invertase (CWINV) genes increased concomitantly with high levels of endogenous Glc and ABA. Furthermore, we showed that in wild type grape berry calli (WT), glucose repressed the expression levels of sucrose synthase (SuSy) and cell wall invertase (CWINV) genes, while ABA increased their expression levels. ABA could not only effectively improve the expression levels of SuSy and CWINV, but also block the repression induced by glucose on the expression of both genes. However, after silencing CsHXK1 or CsHXK2 in grape calli, SuSy and CWINV expression were enhanced, and the expressions of the two genes are insensitive in response to Glc treatment. Interestingly, exogenous ABA alone could not or less increase SuSy and CWINV expression in silencing CsHXK1 or CsHXK2 grape calli compared to WT. Meantime, ABA could not block the repression induced by glucose on the expression of SuSy and CWINV in CsHXK1 or CsHXK2 mutants. Therefore, Glc signal transduction depends on the regulation of CsHXK1 or CsHXK2. ABA signal was also disturbed by CsHXK1 or CsHXK2 silencing. The present results provide new insights into the regulatory role of Glc and ABA on the enzymes related to sugar metabolism in grape berry.

Monoterpenoid Indole Alkaloids from Kopsia officinalis and the Immunosuppressive Activity of Rhazinilam.

Six new monoterpenoid indole alkaloids, kopsinidines C-E (1-3), 11,12-methylenedioxychanofruticosinic acid (4), 12-methoxychanofruticosinic acid (5), and N(4)-methylkopsininate (7), as well as chanofruticosinic acid (6, as a natural product) and 23 known alkaloids, were obtained from the twigs and leaves of Kopsia officinalis. Their structures were characterized by physical data analysis. All isolated compounds were evaluated for their immunosuppressive activity on human T cell proliferation. Rhazinilam (29) significantly inhibited human T cell proliferation activated by anti-CD3/anti-CD28 antibodies (IC50 = 1.0 µM) and alloantigen stimulation (IC50 = 1.1 µM) without obvious cytotoxicity for naïve human T cells and peripheral blood mononuclear cells (0-320 µM). Although it did not affect T cell activation, it induced T cell cycle arrest in the G2/M phase and inhibited proinflammatory cytokine production in activated T cells.

[A new cytotoxic isocoumarin from endophytic fungus Aspergillus versicolor].

A new isocoumarin, along with five known ones,were isolated from the fermentation products of an endophytic fungus Aspergillus versicolorby using various chromatographic techniques.Their structures were elucidated on the basis of extensivespectroscopic analysis, including 1D-and 2D-NMR techniques. Compound 1 was evaluated for cytotoxicity against five human tumor cell lines. The results showed that 1 exhibited weak cytotoxicityagainst NB4, SHSY5Y and MCF7 cells with IC50 values of 6.8, 4.3,8.8 µmol•L⁻¹, respectively.

7,8-Secolignans from the fruits of Schisandra neglecta.

Two new 7,8-secolignans, neglectahenols E and F (1 and 2), together with four known 7,8-secolignans (3-6), were isolated from the fruits of Schisandra neglecta. The structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-6 were tested for their anti-tobacco mosaic virus (anti-TMV) activities at the concentration of 20 µM. Compounds 1 and 6 showed high anti-TMV activities with inhibition rates of 38.2% and 32.7%, respectively. These rates are higher than that of a positive control. Compounds 2-5 also showed modest anti-TMV activities with inhibition rates in the range of 22.8-28.7%. These rates are close to that of a positive control.

[Phenylpropanoids and phenylethanol from flowers of Rosa rugosa].

A new phenylpropanoid (1), together with seven known ones (2-8), has been isolated from the flowers of Rosa rugosa collected from Shanxi province by using various chromatographic techniques. Compound 1 is a new compound, and it displayed cytotoxicity against NB4, SH-SY5Y, PC3, A549 and MCF7 cell lines with IC50 values of 8.2, 6.2, 4.3, 2.8, and 9.6 µmol · L⁻¹ respectively.

[A new flavone from stems of Garcinia bracteata and its anti-TMV activity].

A phytochemical investigation on the stems of Garcinia bracteata collected from Xishuangbanna resulted in the isolation of a new flavone. By analysis of the HRESIMS, IR, UV, 1D and 2D NMR spectra, the structure of the new compound was determined as 7-methoxy-4',6-dihydroxy-8-isobutyryl-flavone(1). Compound 1 was also tested for its anti-tobacco mosaic virus(TMV) activity. Results suggested the 1 possessed remarkable anti-TMV activity, with an inhibition rate of 28.2%.

2-(1H-Benzimidazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol, a benzimidazole derivative, inhibits T cell proliferation involving H+/K+-ATPase inhibition.

In this study, a benzimidazole derivative named BMT-1 is revealed as a potential immunomodulatory agent. BMT-1 inhibits the activity of H+/K+-ATPases from anti-CD3/CD28 activated T cells. Furthermore, inhibition the H+/K+-ATPases by use of BMT-1 should lead to intracellular acidification, inhibiting T cell proliferation. To explore this possibility, the effect of BMT-1 on intracellular pH changes was examined by using BCECF as a pH-dependent fluorescent dye. Interestingly, increases in the pHi were observed in activated T cells, and T cells treated with BMT-1 showed a more acidic intracellular pH. Finally, BMT-1 targeted the H+/K+-ATPases and inhibited the proliferative response of anti-CD3/CD28-stimulated T cells. A cell cycle analysis indicated that BMT-1 arrested the cell cycle progression of activated T cells from the G1 to the S phase without affecting CD25 expression or interleukin-2 (IL-2) production; treating IL-2-dependent PBMCs with BMT-1 also led to the inhibition of cell proliferation. Taken together, these findings demonstrate that BMT-1 inhibits the proliferation of T cells by interfering with H+/K+-ATPases and down-regulating intracellular pHi. This molecule may be an interesting lead compound for the development of new immunomodulatory agents.

Correlation between different points on the face and the width of maxillary anterior teeth.

Statement of problem: There is currently no consensus on the relationship between maxillary anterior teeth and different facial anthropometric measurements. Additionally, whether these relationships vary by age and sex remains unreported. Purpose: This clinical study aimed to investigate the relationship between the intercanine distance (ICaD) and intercanthal distance (ICD), interpupillary distance (IPD), interalar width (IAW), and intercommissural width (ICW), and to compare whether these relationships differ between different age and sex populations. Material and methods: Participants (n = 409) were enrolled according to the inclusion criteria, and their standardized digital images were taken to measure facial and oral segments through an image processing program. The differences between ICaD and four facial measurements and the sexual differences for all measurements were compared using the 1-sample t-test. The differences among different age groups for all measurements were compared using the one-way analysis of variance (ANOVA) test, and a least significant difference (LSD) test was used for multiple comparisons. The association between ICaD and the four facial measurements was evaluated using Pearson correlation analysis. The correlation between ICaD and four facial measurements was evaluated using linear regression. Differences in regression equations among the subgroups were evaluated through subgroup regression analysis and the significance test of the difference between the two regression coefficients. Tests of significance were two-sided, with alpha level of 0.05. The reliability of the results was evaluated by calculating intraclass correlation coefficients. Results: The ICD, IPD, ICW, and IAW significantly differed from the ICaD in both sexes (P < 0.01). All measurements were significantly greater in men than in women (P < 0.01). The differences among the age groups were statistically significant for all measurements except IPD (P < 0.05). A significant positive correlation was found between all facial measurements (r = 0.258 [ICD], r = 0.334 [IPD], r = 0.389 [ICW], and r = 0.393 [IAW]) and the ICaD in both sexes. The highest correlation was found between ICW(r = 0.345) and ICAD in men and IAW (r = 0.285) and ICAD in women. Except for the 20-29 and 50-59 age groups, the mathematical equations of ICaD and facial anthropometric measurements differed among the other age groups and sexes. Conclusions: ICD, IPD, ICW, and IAW cannot be directly used to determine ICaD in both sexes. Nevertheless, when observed from the frontal aspect, by the use of digital images, all facial measurements correlated to the intercanine distance, with a high probability. The mathematical formulae combined with facial anthropological measurements can help ensure the combined width of the six maxillary anterior teeth, but the effects of sex and age differences should be considered.

Immunosuppressive alkaloids from Narcissus tazetta subsp. Chinensis and the mechanism of (+)-narciclasine in vitro and in vivo.

Three previously undescribed and sixteen known alkaloids were bioguidedly isolated from the bulbs of Narcissus tazetta subsp. chinensis (M.Roem.) Masamura & Yanagih. The structures were elucidated by spectroscopic data, including HRESIMS, NMR, and ECD. Eleven of the isolated alkaloids exhibited immunosuppressive activity on the proliferation of human T cells. (+)-Narciclasine (18) showed the most significantly suppressive activity with an IC50 value of 14 ± 5 nM. In vitro, (+)-narciclasine (18) blocked NF-κB signal transduction, but did not affect PI3K/AKT signal transduction. What was more, (+)-narciclasine significantly reduced ALT and AST levels and alleviated liver damage induced by ConA in AIH mouse model.

Quantitative spectroscopic analysis of heterogeneous mixtures: the correction of multiplicative effects caused by variations in physical properties of samples.

Spectral measurements of complex heterogeneous types of mixture samples are often affected by significant multiplicative effects resulting from light scattering, due to physical variations (e.g., particle size and shape, sample packing, and sample surface, etc.) inherent within the individual samples. Therefore, the separation of the spectral contributions due to variations in chemical compositions from those caused by physical variations is crucial to accurate quantitative spectroscopic analysis of heterogeneous samples. In this work, an improved strategy has been proposed to estimate the multiplicative parameters accounting for multiplicative effects in each measured spectrum and, hence, mitigate the detrimental influence of multiplicative effects on the quantitative spectroscopic analysis of heterogeneous samples. The basic assumption of the proposed method is that light scattering due to physical variations has the same effects on the spectral contributions of each of the spectroscopically active chemical components in the same sample mixture. On the basis of this underlying assumption, the proposed method realizes the efficient estimation of the multiplicative parameters by solving a simple quadratic programming problem. The performance of the proposed method has been tested on two publicly available benchmark data sets (i.e., near-infrared total diffuse transmittance spectra of four-component suspension samples and near-infrared spectral data of meat samples) and compared with some empirical approaches designed for the same purpose. It was found that the proposed method provided appreciable improvement in quantitative spectroscopic analysis of heterogeneous mixture samples. The study indicates that accurate quantitative spectroscopic analysis of heterogeneous mixture samples can be achieved through the combination of spectroscopic techniques with smart modeling methodology.

Quantitative analysis of powder mixtures by Raman spectrometry: the influence of particle size and its correction.

Particle size distribution and compactness have significant confounding effects on Raman signals of powder mixtures, which cannot be effectively modeled or corrected by traditional multivariate linear calibration methods such as partial least-squares (PLS), and therefore greatly deteriorate the predictive abilities of Raman calibration models for powder mixtures. The ability to obtain directly quantitative information from Raman signals of powder mixtures with varying particle size distribution and compactness is, therefore, of considerable interest. In this study, an advanced quantitative Raman calibration model was developed to explicitly account for the confounding effects of particle size distribution and compactness on Raman signals of powder mixtures. Under the theoretical guidance of the proposed Raman calibration model, an advanced dual calibration strategy was adopted to separate the Raman contributions caused by the changes in mass fractions of the constituents in powder mixtures from those induced by the variations in the physical properties of samples, and hence achieve accurate quantitative determination for powder mixture samples. The proposed Raman calibration model was applied to the quantitative analysis of backscatter Raman measurements of a proof-of-concept model system of powder mixtures consisting of barium nitrate and potassium chromate. The average relative prediction error of prediction obtained by the proposed Raman calibration model was less than one-third of the corresponding value of the best performing PLS model for mass fractions of barium nitrate in powder mixtures with variations in particle size distribution, as well as compactness.

Synthesis, characterization, and 3D-FDTD simulation of Ag@SiO2 nanoparticles for shell-isolated nanoparticle-enhanced Raman spectroscopy.

Au-seed Ag-growth nanoparticles of controllable diameter (50-100 nm), and having an ultrathin SiO(2) shell of controllable thickness (2-3 nm), were prepared for shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). Their morphological, optical, and material properties were characterized; and their potential for use as a versatile Raman signal amplifier was investigated experimentally using pyridine as a probe molecule and theoretically by the three-dimensional finite-difference time-domain (3D-FDTD) method. We show that a SiO(2) shell as thin as 2 nm can be synthesized pinhole-free on the Ag surface of a nanoparticle, which then becomes the core. The dielectric SiO(2) shell serves to isolate the Raman-signal enhancing core and prevent it from interfering with the system under study. The SiO(2) shell also hinders oxidation of the Ag surface and nanoparticle aggregation. It significantly improves the stability and reproducibility of surface-enhanced Raman scattering (SERS) signal intensity, which is essential for SERS applications. Our 3D-FDTD simulations show that Ag-core SHINERS nanoparticles yield at least 2 orders of magnitude greater enhancement than Au-core ones when excited with green light on a smooth Ag surface, and thus add to the versatility of our SHINERS method.

Electrospray ionization tandem mass spectrometry of chaetoglobosins.

RATIONALE: Chaetoglobosins are a family of macrocyclic polyketide alkaloids. They possess many similar isomers and exhibit a wide range of biological activities. Thus, there is a need for reliable, fast, and low-cost analysis of this class of compounds. METHODS: A series of seven chaetoglobosins from Chaetomium globosum, including two types of isomers, were investigated using electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS) in both positive- and negative-ion mode. The identity of major product ions was supported by deuterium-labeling experiments. RESULTS: In positive-ion mode, the product ion at m/z 130 is the characteristic ion of the indolyl group. A McLafferty rearrangement might play a significant role in the fragmentation of the macrocycle moiety for most chaetoglobosins and produces two series of characteristic product ions, accompanied by neutral losses. The characteristic product ion at m/z 309 in the MS/MS spectrum of chaetoglobosins E indicates the structure of the cyclic olefinic bond in ring B and can be used to distinguish it from the isomers, chaetoglobosins F(ex) , which has an exocyclic double bond on ring B. In negative-ion mode, the McLafferty rearrangement has an important role in the fragmentation pattern of the macrocycle. Some high-abundance radical ions were detected. The radical product ion at m/z 138 might differentiate chaetoglobosins F and penochalasin F, isomers which have very similar structures. CONCLUSIONS: In summary, complementary information obtained from fragmentation experiments of [M+H](+) and [M-H](-) precursor ions is especially valuable for rapid identification of chaetoglobosins. The high-abundance radical ions in negative-ion mode are also of scientific interest.

19-oxygenated ent-kaurane diterpenoids from Isodon pharicus.

Eight new 19-oxygenated ENT-kaurane diterpenoids were isolated from the aerial parts of Isodon pharicus. Their structures were determined by means of extensive spectroscopic techniques including interpretation of 1D and 2D NMR spectra. Selected compounds were evaluated for their cytotoxicity against NB4, A549, PC-3, MCF-7, and SH-SY5Y cell lines.

HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus.

Diabetes, a disease characterized by hyperglycemia, has a serious impact on the lives and families of patients as well as on society. Diabetes is a group of highly heterogeneous metabolic diseases that can be classified as type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), or other according to the etiology. The clinical manifestations are more or less similar among the different types of diabetes, and each type is highly heterogeneous due to different pathogenic factors. Therefore, distinguishing between various types of diabetes and defining their subtypes are major challenges hindering the precise treatment of the disease. T2D is the main type of diabetes in humans as well as the most heterogeneous. Fortunately, some studies have shown that variants of certain genes involved in monogenic diabetes also increase the risk of T2D. We hope this finding will enable breakthroughs regarding the pathogenesis of T2D and facilitate personalized treatment of the disease by exploring the function of the signal genes involved. Hepatocyte nuclear factor 1 homeobox A (HNF1α) is widely expressed in pancreatic ß cells, the liver, the intestines, and other organs. HNF1α is highly polymorphic, but lacks a mutation hot spot. Mutations can be found at any site of the gene. Some single nucleotide polymorphisms (SNPs) cause maturity-onset diabetes of the young type 3 (MODY3) while some others do not cause MODY3 but increase the susceptibility to T2D or GDM. The phenotypes of MODY3 caused by different SNPs also differ. MODY3 is among the most common types of MODY, which is a form of monogenic diabetes mellitus caused by a single gene mutation. Both T2D and GDM are multifactorial diseases caused by both genetic and environmental factors. Different types of diabetes mellitus have different clinical phenotypes and treatments. This review focuses on HNF1α gene polymorphisms, HNF1A-MODY3, HNF1A-associated T2D and GDM, and the related pathogenesis and treatment methods. We hope this review will provide a valuable reference for the precise and individualized treatment of diabetes caused by abnormal HNF1α by summarizing the clinical heterogeneity of blood glucose abnormalities caused by HNF1α mutation.