Mental Health Across the Life Course: Integrative Neurodevelopmental Research from KazNMU
Postpartum depression (PPD) represents an early developmental inflection point. Affecting approximately 10–20% of women globally, PPD arises from complex interactions among neuroendocrine shifts, inflammatory processes, psychosocial stressors, and genetic susceptibility [1]. A comprehensive appraisal synthesizes epidemiology, diagnostic tools—including the Edinburgh Postnatal Depression Scale—and therapeutic strategies spanning selective serotonin reuptake inhibitors, cognitive behavioral therapy, and interpersonal therapy [1]. Importantly, maternal depression is framed not solely as an individual psychiatric disorder but as a determinant of infant attachment, neurocognitive maturation, and intergenerational mental health risk.
This developmental trajectory extends to autism spectrum disorder (ASD), recognized in ICD-11 as a neurodevelopmental condition affecting roughly 1 in 100 children worldwide. A national cross-sectional survey of 410 adults revealed that only 18.3% were familiar with core ASD symptoms, underscoring sociocultural barriers to early identification [2]. Complementary research involving 390 parents documented structural strain: 25.4% reported leaving employment to provide care, and 73.3% cited insufficient state financial support [3]. Further investigation of 327 parents demonstrated mean wellbeing scores of 52.6 ± 15.65, with disability status significantly predicting lower parental wellbeing (β = 0.20, p < 0.001) and revealing limited preparedness among primary-care psychologists to provide specialized support [4]. Together, these studies construct a socio-ecological understanding of ASD that links awareness, service accessibility, and caregiver resilience.
Translational innovation is evident in a prospective cohort study evaluating a gamified mobile application for children with Level 1 ASD [5]. Within one month, oral hygiene indices improved by 28–52%, plaque and gingival scores declined by over 50%, and 85% of participants achieved greater brushing independence. A strong correlation between usability and behavioral acquisition highlights the potential of structured digital reinforcement to enhance executive functioning and adaptive routines in neurodiverse populations.
Population-level stressors further contextualize vulnerability. A multistage stratified survey of 991 adults during the COVID-19 peak identified depressive symptoms in 12.01% and anxiety in 8.38%, with female gender, food insecurity, healthcare disruption, and family conflict independently associated with elevated risk [6].
Collectively, these investigations articulate an integrative architecture that links maternal neurobiology, child neurodevelopment, caregiver adaptation, digital interventions, and structural determinants. KazNMU’s contribution lies not in isolated findings but in demonstrating how emerging research ecosystems can generate biologically grounded, socially contextualized, and scalable evidence on mental health across the life course.
- Aimagambetova G, et al. Postpartum Depression: Epidemiology, Risk Factors, Diagnosis, and Management. J Clin Med. 2025;14:2418, doi:3390/jcm14072418
- Kurmanalina S, Samambayeva A, Akhtayeva N, Kozhageldiyeva L, Kosherbayeva L. Awareness of Autism Spectrum Disorder Among Population of Kazakhstan. J Autism Dev Disord. 2025;55:2566–2572, doi: 1007/s10803-021-05021-9
- Imamatdinova A, Samambayeva A, Akhtayeva N, et al. Autism Spectrum Disorders: Experience of Parents in Kazakhstan. BMC Public Health. 2025;25:2676, doi: 1186/s12889-025-2676
- Akhtayeva N, Kosherbayeva L, Imamatdinova A, Šmigelskas K. Wellbeing of Parents Raising Children with Autism Spectrum Disorder and the Role of Psychologists. Arch Med Sci. 2025;21(3):858–867, doi: 5114/aoms/190772
- Samambayeva A, et al. Innovative Oral Hygiene Strategies for Children with Autism Spectrum Disorder: A Gamified App-Based Intervention. 2025, doi: 1007/s40368-025-01115-5
- Mergenova G, Rosenthal SL, Myrkassymova A, et al. The COVID-19 Pandemic and Mental Health in Kazakhstan. Cambridge Prisms: Global Mental Health. 2023;10:e52, doi: 1017/gmh.2023.46
From Natural Products to Drug Candidates: A Two-Way Research Model for Future Therapies in Cardiovascular, Arthritis, and Cancer Diseases
Over the past two decades, under the leadership of Professor Yi-Zhun Zhu, researchers at the Macau University of Science and Technology have been focusing on a distinctive bidirectional research model for small molecule drug development. This integrated strategy combines two complementary approaches: “from bioactive natural compounds to novel target identification” and “from novel therapeutic target to new small-molecule development.” Moving beyond conventional linear drug discovery processes, this framework facilitates bidirectional innovation, advancing both fundamental researches and translational applications.
Drug discovery can be conceptualized as an exploration on a vast island. Traditional approaches often follow a single linear route toward therapeutic breakthroughs, namely, the treasure. In contrast, the bidirectional model offers greater flexibility. Investigations may begin with a “coin” already in hand—such as Leonurine (SCM-198), S-Propargyl-Cysteine (SPRC), the natural compounds functioning as a valuable starting point. By studying that coin closely, researchers uncover clues about its origins, which in turn point them toward new biological targets and therapeutic directions, including NOX4, SMYD3, JMJD3, HDAC6 and so on. Alternatively, the journey begins the other way around, with a “map” in hand—a promising biological mechanism such as HDAC6/MyD88/NF-κB signaling pathway or STAT3-NAV2 axis in arthritis, serving as a guide for rational drug design. In both cases, the two pathways converge, leading to synergistic advances in drug discovery.
This strategy has yielded significant milestones, including the industrial translation of first-in-class therapeutics, and continues to drive progress across multiple therapeutic areas. In particular, the model has guided three major research trajectories: starting with leonurine, a natural product with traditional cardiovascular applications that has been advanced into modern drug development; extending into SPRC, a synthetically designed modulator of hydrogen sulfide; and progressing to epigenetic drug discovery through SMYD3 inhibition, a path with implications for vascular aging and oncology. Collectively, these directions illustrate how atural product-derived insights and target-driven design can converge within a single framework to shape the next era of medicine.
From Small molecule-to-Target: Leonurine
The journey along the “small molecule-to-target” pathway began with leonurine, a compound derived from Leonurus japonicus, a plant used in traditional medicine for cardiovascular health and gynecological diseases. What makes Leonurine significant is not only its herbal origins but also its development into a scientifically validated compound with cardioprotective effects, anti-inflammatory properties, pro-angiogenic effects following cardiac injury, and potential applications beyond cardiovascular disease which accounts for 17.9 million annual deaths globally [1] [2,3]. Beyond cardiovascular applications, it has demonstrated efficacy in mitigating endometriosis via modulation of estrogen-mediated immune dysfunction [4], as well as anti-atherosclerotic and hepatoprotective activities [5,6]. The team has also advanced Leonurine into novel formulations, the team developed a sustained-release leonurine formulation using PLGA microspheres encapsulating drug nanocrystals (Leo-nano@MP), which significantly improved lipid metabolism and reduced dosing frequency via subcutaneous administration in a hyperlipidemic rat model, demonstrating high drug loading, prolonged release, and good biocompatibility [7].
This pathway exemplifies how a single bioactive natural product can unravel novel mechanisms and open new therapeutic avenues. Leonurine thus serves as a prototype for transforming traditional herbal compounds into first-in-class therapeutics with validated mechanisms of action.
The translational development of Leonurine is supported by multiple patents from Professor Zhu’s group, covering pharmaceutical formulations and delivery technologies. For example, these include nanoliposome and microsphere systems that enhance bioavailability and enable controlled release, broadening the therapeutic window for cardiovascular and inflammatory diseases. Their patents also highlight leonurine’s role in modulating lipid metabolism, PPARγ pathways, and its use in treating liver disease and inflammation-related disorders. Collectively, these innovations elevate Leonurine from a traditional herbal compound into a modern, patent-protected therapeutic entity with substantial clinical potential.
From Small molecule-to-Target: another example, SPRC and CSE
If Leonurine represents the journey from monomer to target, S-Propargyl-Cysteine (SPRC) illustrates the complementary path—from target to molecule. Here, the therapeutic target is cystathionine Gamma Lyase (CSE), an enzyme that produces the signaling molecule hydrogen sulfide (H₂S) from L-cysteine. SPRC acts as a donor of endogenous H₂S, an endogenous gasotransmitter known for its profound effects on vascular health, inflammation, and longevity. Based on this mechanistic insight, SPRC was designed as a synthetic amino acid derivative that modulates H₂S levels.
Based on Professor Zhu’s studies, SPRC has demonstrated wide-ranging benefits: regulating immune responses, protecting neurons after stroke, and promoting angiogenesis [8,9]. In rheumatoid arthritis (RA), which affects over 18 million people globally [10], SPRC has been shown to rebalance immune cells by inhibiting the JAK/STAT pathway, reducing inflammation and slowing joint damage [11]. Beyond exploring the pharmacological efficacy of SPRC, the team have also engineered SPRC-based nanocarriers and hybrid molecules for precision therapies against RA,
This small molecule-to-target pathway highlights how identifying a novel biological mechanism—in this case, CSE as the target of SPRC—can inspire the rational design of first-in-class therapeutic candidates with translational potential.
Patents filed by Professor Zhu and his team surrounding SPRC and related signaling pathways demonstrate the translational depth of this pathway by engineering innovative drug delivery platforms. Microsphere and mesoporous silica formulations enhance the stability and sustained release of SPRC, improving its therapeutic precision in diseases such as rheumatoid arthritis and ischemic injury. Additionally, their patents on endogenous H₂S donors for RA treatment underscore the progression from mechanistic insight to tangible therapeutic inventions. These intellectual property advances ensure SPRC’s positioning not just as a promising molecule, but as a scalable and clinically adaptable treatment strategy.
Target-to-Molecule: SMYD3 and Epigenetic Regulation
Extending the target-driven approach further, the researchers turned their attention to the epigenetic regulator SMYD3, a histone methyltransferase linked to vascular aging, cellular remodeling, and cancer progression. Unlike Leonurine’s herbal origins, SMYD3 inhibition begins firmly at the target level, with the goal of designing molecules that disrupt pathogenic gene regulation.
Professor Zhu’s research team showed that, through high-throughput screening and structure-based drug design, small molecules such as ZYZ384 were identified to reduce cancer cell proliferation by lowering H3K4 trimethylation on oncogenic promoters. In models of hepatocellular carcinoma, SMYD3 inhibition suppressed tumor growth, offering a new precision epigenetic strategy against cancer [14]. Beyond oncology, targeting SMYD3 also addresses vascular senescence, the progressive aging of blood vessels that underlies hypertension, atherosclerosis, and stroke [15,16].
This work demonstrates how the target-to-molecule pathway can move beyond classical signaling molecules into the realm of epigenetics, opening entirely new frontiers for precision therapies in both cancer and age-related vascular disease.
The translational impact of SMYD3 research is evidenced by patents from Professor Zhu’s team covering novel SMYD3 inhibitors and their use in treating cancer and vascular disorders. These patents protect chemical entities capable of selectively modulating histone methylation, establishing a foundation for first-in-class epigenetic therapeutics in oncology and cardiovascular medicine.
The Bidirectional Model: Advancing Integrated Drug Discovery
Together, these approaches illustrate a cycle of discovery that moves beyond the conventional linear model of drug development. By leveraging natural products for target deconvolution and employing target-based rational design for new chemical entities, this bidirectional framework bridges traditional knowledge and contemporary science, integrating basic research with clinical translation. This model provides a robust and efficient strategy for developing small-molecule therapies that address major unmet medical needs in cardiovascular disease, arthritis, and cancer.
*Notes: This article provides research teasers for each reference to showcase the novelties
List of Patents
Preparation Method and Application of Leonurine Sustained-Release Microspheres
Preparation Method and Application of a Small-Molecule Inhibitor of Histone Methyltransferase SMYD3
Preparation Method of SCM198 Gel for Treating Skin Injuries
Microsphere Formulation Loaded with S-Propargyl-Cysteine and Its Preparation Method
Mesoporous Silica Formulation Loaded with S-Propargyl-Cysteine and Its Preparation Method
Endogenous Hydrogen Sulfide Sustained-Release Formulation: Preparation Method and Application
References
[1] https://www.who.int/health-topics/cardiovascular-diseases
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[10] https://www.who.int/news-room/fact-sheets/detail/rheumatoid-arthritis
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