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  1. Jana S, Do TN, Nowakowski PJ, Khyasudeen MF, Le DV, Lim IJY, et al.
    J Phys Chem B, 2023 Aug 24;127(33):7309-7322.
    PMID: 37579317 DOI: 10.1021/acs.jpcb.3c02521
    In a two-dimensional (2D) optical spectrum of a multilevel system, there are diagonal peaks and off-diagonal cross-peaks that correlate the different levels. The time-dependent properties of these diagonal peaks and cross-peaks contain much information about the dynamics of the multilevel system. The time-dependent diagonal peakshape that depends on the spectral diffusion dynamics of the associated transition and characterized by the frequency-fluctuation correlation function (FFCF) is well studied. However, the time-dependent peakshape of a cross-peak that provides the correlation dynamics between different transitions is much less studied or understood. We derived the third-order nonlinear response functions that describe the cross-peaks in a 2D electronic spectrum of a multilevel system that arise from processes sharing a common ground state and/or from internal conversion and population transfer. We can use the center line slope (CLS) analysis to characterize the cross-peaks in conjunction with the diagonal peaks. This allows us to recover the frequency-fluctuation cross-correlation functions (FXCFs) between two transitions. The FXCF and its subsidiary quantities such as the initial correlation and the initial covariance between different transitions are important for studying the correlation effects between states in complex systems, such as energy-transfer processes. Furthermore, knowledge of how various molecular processes over different timescales affect simultaneously different transitions can also be obtained from the measured FXCF. We validated and tested our derived equations and analysis process by studying, as an example, the 2D electronic spectra of metal-free phthalocyanine in solution. We measured and analyzed the diagonal peaks of the Qx and Qy transitions and the cross-peaks between these two transitions of this multilevel electronic system and obtained the associated FFCFs and FXCFs. In this model system, we measured negative components of FXCF over the tens of picosecond timescale. This suggests that in phthalocyanine, the Qx and Qy transitions coupling with the solvent molecule motion are anticorrelated to each other.
  2. Jana S, Gayen S, Gupta BD, Singha S, Mondal J, Kar A, et al.
    PMID: 37691221 DOI: 10.2174/1871530323666230907115818
    BACKGROUND: The medicinal plants of the Cucurbitaceae family, such as Solena heterophylla Lour. fruits, have significant ethnobotanical value and are readily accessible in North East India.

    AIMS: We conducted a study on Solena heterophylla Lour. fruits to evaluate their anti-diabetic activity in vivo, standardize their HPTLC, and profile their metabolites using LC-QTOF-MS. We aimed to explore the molecular mechanism behind their effects on oxidative stress and glycosylated hemoglobin (HbA1c).

    METHODS: Firstly, the ethyl acetate fraction of Solena heterophylla Lour. fruits was standardized using Cucurbitacin B as a standard marker by conducting HPTLC evaluation. Next, we delved into analyzing metabolite profiling. In addition, the standardized fraction was utilized in an experimental study to investigate the molecular mechanism of action in an in vivo high-fat diet and a low dose of streptozotocin-induced diabetic model.

    RESULTS: We have reportedly identified 52 metabolites in the ethyl acetate fraction of Solena heterophylla (EASH). In the in vitro tests, it has been observed that this extract from plants possesses notable inhibitory properties against α-amylase and α-glucosidase. Solena heterophylla fruits with high levels of Cucurbitacin B (2.29% w/w) helped lower FBG levels in animals with EASH treatment. EASH treatment reduced HbA1c levels and normalized liver lipid peroxidation and antioxidant enzyme levels. SGOT, SGPT, and SALP serum enzyme levels also returned to normal.

    CONCLUSION: Based on the current evaluation, it was found that EASH exhibited encouraging hypoglycemic effects in diabetic rats induced by a low dose of STZ and high-fat diet, which warrants further investigation.

  3. Schaefer R, Amparo da Costa Leite PH, Silva R, Abdool Karim Q, Akolo C, Cáceres CF, et al.
    Lancet HIV, 2022 Apr;9(4):e242-e253.
    PMID: 35271825 DOI: 10.1016/S2352-3018(22)00004-2
    BACKGROUND: Previous WHO guidance on tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis (PrEP) suggests measuring creatinine levels at PrEP initiation and regularly afterwards, which might represent barriers to PrEP implementation and uptake. We aimed to systematically review published literature on kidney toxicity among tenofovir disoproxil fumarate-based oral PrEP users and conducted an individual participant data meta-analysis (IPDMA) on kidney function among PrEP users in a global implementation project dataset.

    METHODS: In this systematic review and meta-analysis we searched PubMed up to June 30, 2021, for randomised controlled trials (RCTs) or cohort studies that reported on graded kidney-related adverse events among oral PrEP users (tenofovir disoproxil fumarate-based PrEP alone or in combination with emtricitabine or lamivudine). We extracted summary data and conducted meta-analyses with random-effects models to estimate relative risks of grade 1 and higher and grade 2 and higher kidney-related adverse events, measured by elevated serum creatinine or decline in estimated creatinine clearance or estimated glomerular filtration rate. The IPDMA included (largely unpublished) individual participant data from 17 PrEP implementation projects and two RCTs. Estimated baseline creatinine clearance and creatinine clearance change after initiation were described by age, gender, and comorbidities. We used random-effects regressions to estimate the risk in decline of creatinine clearance to less than 60 mL/min.

    FINDINGS: We identified 62 unique records and included 17 articles reporting on 11 RCTs with 13 523 participants in meta-analyses. PrEP use was associated with increased risk of grade 1 and higher kidney adverse events (pooled odds ratio [OR] 1·49, 95% CI 1·22-1·81; I2=25%) and grade 2 and higher events (OR 1·75, 0·68-4·49; I2=0%), although the grade 2 and higher association was not statistically significant and events were rare (13 out of 6764 in the intervention group vs six out of 6782 in the control group). The IPDMA included 18 676 individuals from 15 countries (1453 [7·8%] from RCTs) and 79 (0·42%) had a baseline estimated creatinine clearance of less than 60 mL/min (increasing proportions with increasing age). Longitudinal analyses included 14 368 PrEP users and 349 (2·43%) individuals had a decline to less than 60 mL/min creatinine clearance, with higher risks associated with increasing age and baseline creatinine clearance of 60·00-89·99 mL/min (adjusted hazard ratio [aHR] 8·49, 95% CI 6·44-11·20) and less than 60 mL/min (aHR 20·83, 12·83-33·82).

    INTERPRETATION: RCTs suggest that risks of kidney-related adverse events among tenofovir disoproxil fumarate-based oral PrEP users are increased but generally mild and small. Our global PrEP user analysis found varying risks by age and baseline creatinine clearance. Kidney function screening and monitoring might focus on older individuals, those with baseline creatinine clearance of less than 90 mL/min, and those with kidney-related comorbidities. Less frequent or optional screening among younger individuals without kidney-related comorbidities may reduce barriers to PrEP implementation and use.

    FUNDING: Unitaid, Bill & Melinda Gates Foundation, WHO.

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